Interaction between Neuromelanin and Alpha-Synuclein in Parkinson’s Disease
Identifieur interne : 000035 ( Pmc/Corpus ); précédent : 000034; suivant : 000036Interaction between Neuromelanin and Alpha-Synuclein in Parkinson’s Disease
Auteurs : Shengli Xu ; Piu ChanSource :
- Biomolecules [ 2218-273X ] ; 2015.
Abstract
Parkinson’s disease (PD) is a very common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) into Lewy body (LB) inclusions and the loss of neuronmelanin (NM) containing dopamine (DA) neurons in the substantia nigra (SN). Pathological α-syn and NM are two prominent hallmarks in this selective and progressive neurodegenerative disease. Pathological α-syn can induce dopaminergic neuron death by various mechanisms, such as inducing oxidative stress and inhibiting protein degradation systems. Therefore, to explore the factors that trigger α-syn to convert from a non-toxic protein to toxic one is a pivotal question to clarify the mechanisms of PD pathogenesis. Many triggers for pathological α-syn aggregation have been identified, including missense mutations in the α-syn gene, higher concentration, and posttranslational modifications of α-Syn. Recently, the role of NM in inducing α-syn expression and aggregation has been suggested as a mechanism for this pigment to modulate neuronal vulnerability in PD. NM may be responsible for PD and age-associated increase and aggregation in α-syn. Here, we reviewed our previous study and other recent findings in the area of interaction between NM and α-syn.
Url:
DOI: 10.3390/biom5021122
PubMed: 26057626
PubMed Central: 4496713
Links to Exploration step
PMC:4496713Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Interaction between Neuromelanin and Alpha-Synuclein in Parkinson’s Disease</title><author><name sortKey="Xu, Shengli" sort="Xu, Shengli" uniqKey="Xu S" first="Shengli" last="Xu">Shengli Xu</name><affiliation><nlm:aff id="af1-biomolecules-05-01122">Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences, No.45 changchun St., Xicheng District, Beijing 100053, China; E-Mail:<email>xushngli_xw@163.com</email></nlm:aff></affiliation><affiliation><nlm:aff id="af2-biomolecules-05-01122">Parkinson’s disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China</nlm:aff></affiliation></author><author><name sortKey="Chan, Piu" sort="Chan, Piu" uniqKey="Chan P" first="Piu" last="Chan">Piu Chan</name><affiliation><nlm:aff id="af1-biomolecules-05-01122">Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences, No.45 changchun St., Xicheng District, Beijing 100053, China; E-Mail:<email>xushngli_xw@163.com</email></nlm:aff></affiliation><affiliation><nlm:aff id="af2-biomolecules-05-01122">Parkinson’s disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26057626</idno><idno type="pmc">4496713</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496713</idno><idno type="RBID">PMC:4496713</idno><idno type="doi">10.3390/biom5021122</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000035</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000035</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Interaction between Neuromelanin and Alpha-Synuclein in Parkinson’s Disease</title><author><name sortKey="Xu, Shengli" sort="Xu, Shengli" uniqKey="Xu S" first="Shengli" last="Xu">Shengli Xu</name><affiliation><nlm:aff id="af1-biomolecules-05-01122">Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences, No.45 changchun St., Xicheng District, Beijing 100053, China; E-Mail:<email>xushngli_xw@163.com</email></nlm:aff></affiliation><affiliation><nlm:aff id="af2-biomolecules-05-01122">Parkinson’s disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China</nlm:aff></affiliation></author><author><name sortKey="Chan, Piu" sort="Chan, Piu" uniqKey="Chan P" first="Piu" last="Chan">Piu Chan</name><affiliation><nlm:aff id="af1-biomolecules-05-01122">Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences, No.45 changchun St., Xicheng District, Beijing 100053, China; E-Mail:<email>xushngli_xw@163.com</email></nlm:aff></affiliation><affiliation><nlm:aff id="af2-biomolecules-05-01122">Parkinson’s disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China</nlm:aff></affiliation></author></analytic><series><title level="j">Biomolecules</title><idno type="eISSN">2218-273X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Parkinson’s disease (PD) is a very common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) into Lewy body (LB) inclusions and the loss of neuronmelanin (NM) containing dopamine (DA) neurons in the substantia nigra (SN). Pathological α-syn and NM are two prominent hallmarks in this selective and progressive neurodegenerative disease. Pathological α-syn can induce dopaminergic neuron death by various mechanisms, such as inducing oxidative stress and inhibiting protein degradation systems. Therefore, to explore the factors that trigger α-syn to convert from a non-toxic protein to toxic one is a pivotal question to clarify the mechanisms of PD pathogenesis. Many triggers for pathological α-syn aggregation have been identified, including missense mutations in the α-syn gene, higher concentration, and posttranslational modifications of α-Syn. Recently, the role of NM in inducing α-syn expression and aggregation has been suggested as a mechanism for this pigment to modulate neuronal vulnerability in PD. NM may be responsible for PD and age-associated increase and aggregation in α-syn. Here, we reviewed our previous study and other recent findings in the area of interaction between NM and α-syn.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Olanow, C W" uniqKey="Olanow C">C.W. Olanow</name></author><author><name sortKey="Tatton, W G" uniqKey="Tatton W">W.G. Tatton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author><author><name sortKey="Surmeier, D J" uniqKey="Surmeier D">D.J. Surmeier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fahn, S" uniqKey="Fahn S">S. Fahn</name></author><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poewe, W" uniqKey="Poewe W">W. Poewe</name></author><author><name sortKey="Antonini, A" uniqKey="Antonini A">A. Antonini</name></author><author><name sortKey="Zijlmans, J C" uniqKey="Zijlmans J">J.C. Zijlmans</name></author><author><name sortKey="Burkhard, P R" uniqKey="Burkhard P">P.R. Burkhard</name></author><author><name sortKey="Vingerhoets, F" uniqKey="Vingerhoets F">F. Vingerhoets</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gonera, E G" uniqKey="Gonera E">E.G. Gonera</name></author><author><name sortKey="Van Hof, M" uniqKey="Van Hof M">M. Van’t Hof</name></author><author><name sortKey="Berger, H J" uniqKey="Berger H">H.J. Berger</name></author><author><name sortKey="Van Weel, C" uniqKey="Van Weel C">C. van Weel</name></author><author><name sortKey="Horstink, M W" uniqKey="Horstink M">M.W. Horstink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ziemssen, T" uniqKey="Ziemssen T">T. Ziemssen</name></author><author><name sortKey="Reichmann, H" uniqKey="Reichmann H">H. Reichmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maass, A" uniqKey="Maass A">A. Maass</name></author><author><name sortKey="Reichmann, H" uniqKey="Reichmann H">H. Reichmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jenner, P" uniqKey="Jenner P">P. Jenner</name></author><author><name sortKey="Morris, H R" uniqKey="Morris H">H.R. Morris</name></author><author><name sortKey="Robbins, T W" uniqKey="Robbins T">T.W. Robbins</name></author><author><name sortKey="Goedert, M" uniqKey="Goedert M">M. Goedert</name></author><author><name sortKey="Hardy, J" uniqKey="Hardy J">J. Hardy</name></author><author><name sortKey="Ben Shlomo, Y" uniqKey="Ben Shlomo Y">Y. Ben-Shlomo</name></author><author><name sortKey="Bolam, P" uniqKey="Bolam P">P. Bolam</name></author><author><name sortKey="Burn, D" uniqKey="Burn D">D. Burn</name></author><author><name sortKey="Hindle, J V" uniqKey="Hindle J">J.V. Hindle</name></author><author><name sortKey="Brooks, D" uniqKey="Brooks D">D. Brooks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Polymeropoulos, M H" uniqKey="Polymeropoulos M">M.H. Polymeropoulos</name></author><author><name sortKey="Lavedan, C" uniqKey="Lavedan C">C. Lavedan</name></author><author><name sortKey="Leroy, E" uniqKey="Leroy E">E. Leroy</name></author><author><name sortKey="Ide, S E" uniqKey="Ide S">S.E. Ide</name></author><author><name sortKey="Dehejia, A" uniqKey="Dehejia A">A. Dehejia</name></author><author><name sortKey="Dutra, A" uniqKey="Dutra A">A. Dutra</name></author><author><name sortKey="Pike, B" uniqKey="Pike B">B. Pike</name></author><author><name sortKey="Root, H" uniqKey="Root H">H. Root</name></author><author><name sortKey="Rubenstein, J" uniqKey="Rubenstein J">J. Rubenstein</name></author><author><name sortKey="Boyer, R" uniqKey="Boyer R">R. Boyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singleton, A B" uniqKey="Singleton A">A.B. Singleton</name></author><author><name sortKey="Farrer, M" uniqKey="Farrer M">M. Farrer</name></author><author><name sortKey="Johnson, J" uniqKey="Johnson J">J. Johnson</name></author><author><name sortKey="Singleton, A" uniqKey="Singleton A">A. Singleton</name></author><author><name sortKey="Hague, S" uniqKey="Hague S">S. Hague</name></author><author><name sortKey="Kachergus, J" uniqKey="Kachergus J">J. Kachergus</name></author><author><name sortKey="Hulihan, M" uniqKey="Hulihan M">M. Hulihan</name></author><author><name sortKey="Peuralinna, T" uniqKey="Peuralinna T">T. Peuralinna</name></author><author><name sortKey="Dutra, A" uniqKey="Dutra A">A. Dutra</name></author><author><name sortKey="Nussbaum, R" uniqKey="Nussbaum R">R. Nussbaum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zimprich, A" uniqKey="Zimprich A">A. Zimprich</name></author><author><name sortKey="Biskup, S" uniqKey="Biskup S">S. Biskup</name></author><author><name sortKey="Leitner, P" uniqKey="Leitner P">P. Leitner</name></author><author><name sortKey="Lichtner, P" uniqKey="Lichtner P">P. Lichtner</name></author><author><name sortKey="Farrer, M" uniqKey="Farrer M">M. Farrer</name></author><author><name sortKey="Lincoln, S" uniqKey="Lincoln S">S. Lincoln</name></author><author><name sortKey="Kachergus, J" uniqKey="Kachergus J">J. Kachergus</name></author><author><name sortKey="Hulihan, M" uniqKey="Hulihan M">M. Hulihan</name></author><author><name sortKey="Uitti, R J" uniqKey="Uitti R">R.J. Uitti</name></author><author><name sortKey="Calne, D B" uniqKey="Calne D">D.B. Calne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Westbroek, W" uniqKey="Westbroek W">W. Westbroek</name></author><author><name sortKey="Gustafson, A M" uniqKey="Gustafson A">A.M. Gustafson</name></author><author><name sortKey="Sidransky, E" uniqKey="Sidransky E">E. Sidransky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gouider Khouja, N" uniqKey="Gouider Khouja N">N. Gouider-Khouja</name></author><author><name sortKey="Larnaout, A" uniqKey="Larnaout A">A. Larnaout</name></author><author><name sortKey="Amouri, R" uniqKey="Amouri R">R. Amouri</name></author><author><name sortKey="Sfar, S" uniqKey="Sfar S">S. Sfar</name></author><author><name sortKey="Belal, S" uniqKey="Belal S">S. Belal</name></author><author><name sortKey="Ben Hamida, C" uniqKey="Ben Hamida C">C. Ben Hamida</name></author><author><name sortKey="Ben Hamida, M" uniqKey="Ben Hamida M">M. Ben Hamida</name></author><author><name sortKey="Hattori, N" uniqKey="Hattori N">N. Hattori</name></author><author><name sortKey="Mizuno, Y" uniqKey="Mizuno Y">Y. Mizuno</name></author><author><name sortKey="Hentati, F" uniqKey="Hentati F">F. Hentati</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonifati, V" uniqKey="Bonifati V">V. Bonifati</name></author><author><name sortKey="Rizzu, P" uniqKey="Rizzu P">P. Rizzu</name></author><author><name sortKey="Van Baren, M J" uniqKey="Van Baren M">M.J. van Baren</name></author><author><name sortKey="Schaap, O" uniqKey="Schaap O">O. Schaap</name></author><author><name sortKey="Breedveld, G J" uniqKey="Breedveld G">G.J. Breedveld</name></author><author><name sortKey="Krieger, E" uniqKey="Krieger E">E. Krieger</name></author><author><name sortKey="Dekker, M C" uniqKey="Dekker M">M.C. Dekker</name></author><author><name sortKey="Squitieri, F" uniqKey="Squitieri F">F. Squitieri</name></author><author><name sortKey="Ibanez, P" uniqKey="Ibanez P">P. Ibanez</name></author><author><name sortKey="Joosse, M" uniqKey="Joosse M">M. Joosse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Valente, E M" uniqKey="Valente E">E.M. Valente</name></author><author><name sortKey="Abou Sleiman, P M" uniqKey="Abou Sleiman P">P.M. Abou-Sleiman</name></author><author><name sortKey="Caputo, V" uniqKey="Caputo V">V. Caputo</name></author><author><name sortKey="Muqit, M M" uniqKey="Muqit M">M.M. Muqit</name></author><author><name sortKey="Harvey, K" uniqKey="Harvey K">K. Harvey</name></author><author><name sortKey="Gispert, S" uniqKey="Gispert S">S. Gispert</name></author><author><name sortKey="Ali, Z" uniqKey="Ali Z">Z. Ali</name></author><author><name sortKey="Del Turco, D" uniqKey="Del Turco D">D. del Turco</name></author><author><name sortKey="Bentivoglio, A R" uniqKey="Bentivoglio A">A.R. Bentivoglio</name></author><author><name sortKey="Healy, D G" uniqKey="Healy D">D.G. Healy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamza, T H" uniqKey="Hamza T">T.H. Hamza</name></author><author><name sortKey="Zabetian, C P" uniqKey="Zabetian C">C.P. Zabetian</name></author><author><name sortKey="Tenesa, A" uniqKey="Tenesa A">A. Tenesa</name></author><author><name sortKey="Laederach, A" uniqKey="Laederach A">A. Laederach</name></author><author><name sortKey="Montimurro, J" uniqKey="Montimurro J">J. Montimurro</name></author><author><name sortKey="Yearout, D" uniqKey="Yearout D">D. Yearout</name></author><author><name sortKey="Kay, D M" uniqKey="Kay D">D.M. Kay</name></author><author><name sortKey="Doheny, K F" uniqKey="Doheny K">K.F. Doheny</name></author><author><name sortKey="Paschall, J" uniqKey="Paschall J">J. Paschall</name></author><author><name sortKey="Pugh, E" uniqKey="Pugh E">E. Pugh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skipper, L" uniqKey="Skipper L">L. Skipper</name></author><author><name sortKey="Wilkes, K" uniqKey="Wilkes K">K. Wilkes</name></author><author><name sortKey="Toft, M" uniqKey="Toft M">M. Toft</name></author><author><name sortKey="Baker, M" uniqKey="Baker M">M. Baker</name></author><author><name sortKey="Lincoln, S" uniqKey="Lincoln S">S. Lincoln</name></author><author><name sortKey="Hulihan, M" uniqKey="Hulihan M">M. Hulihan</name></author><author><name sortKey="Ross, O A" uniqKey="Ross O">O.A. Ross</name></author><author><name sortKey="Hutton, M" uniqKey="Hutton M">M. Hutton</name></author><author><name sortKey="Aasly, J" uniqKey="Aasly J">J. Aasly</name></author><author><name sortKey="Farrer, M" uniqKey="Farrer M">M. Farrer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jensen, P H" uniqKey="Jensen P">P.H. Jensen</name></author><author><name sortKey="Nielsen, M S" uniqKey="Nielsen M">M.S. Nielsen</name></author><author><name sortKey="Jakes, R" uniqKey="Jakes R">R. Jakes</name></author><author><name sortKey="Dotti, C G" uniqKey="Dotti C">C.G. Dotti</name></author><author><name sortKey="Goedert, M" uniqKey="Goedert M">M. Goedert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Farrer, M" uniqKey="Farrer M">M. Farrer</name></author><author><name sortKey="Wavrant De Vrieze, F" uniqKey="Wavrant De Vrieze F">F. Wavrant-De Vrieze</name></author><author><name sortKey="Crook, R" uniqKey="Crook R">R. Crook</name></author><author><name sortKey="Boles, L" uniqKey="Boles L">L. Boles</name></author><author><name sortKey="Perez Tur, J" uniqKey="Perez Tur J">J. Perez-Tur</name></author><author><name sortKey="Hardy, J" uniqKey="Hardy J">J. Hardy</name></author><author><name sortKey="Johnson, W G" uniqKey="Johnson W">W.G. Johnson</name></author><author><name sortKey="Steele, J" uniqKey="Steele J">J. Steele</name></author><author><name sortKey="Maraganore, D" uniqKey="Maraganore D">D. Maraganore</name></author><author><name sortKey="Gwinn, K" uniqKey="Gwinn K">K. Gwinn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zarranz, J J" uniqKey="Zarranz J">J.J. Zarranz</name></author><author><name sortKey="Alegre, J" uniqKey="Alegre J">J. Alegre</name></author><author><name sortKey="G Mez Esteban, J C" uniqKey="G Mez Esteban J">J.C. Gómez-Esteban</name></author><author><name sortKey="Lezcano, E" uniqKey="Lezcano E">E. Lezcano</name></author><author><name sortKey="Ros, R" uniqKey="Ros R">R. Ros</name></author><author><name sortKey="Ampuero, I" uniqKey="Ampuero I">I. Ampuero</name></author><author><name sortKey="Vidal, L" uniqKey="Vidal L">L. Vidal</name></author><author><name sortKey="Hoenicka, J" uniqKey="Hoenicka J">J. Hoenicka</name></author><author><name sortKey="Rodriguez, O" uniqKey="Rodriguez O">O. Rodriguez</name></author><author><name sortKey="Atares, B" uniqKey="Atares B">B. Atarés</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Proukakis, C" uniqKey="Proukakis C">C. Proukakis</name></author><author><name sortKey="Dudzik, C G" uniqKey="Dudzik C">C.G. Dudzik</name></author><author><name sortKey="Brier, T" uniqKey="Brier T">T. Brier</name></author><author><name sortKey="Mackay, D S" uniqKey="Mackay D">D.S. MacKay</name></author><author><name sortKey="Cooper, J M" uniqKey="Cooper J">J.M. Cooper</name></author><author><name sortKey="Millhauser, G L" uniqKey="Millhauser G">G.L. Millhauser</name></author><author><name sortKey="Houlden, H" uniqKey="Houlden H">H. Houlden</name></author><author><name sortKey="Schapira, A H" uniqKey="Schapira A">A.H. Schapira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kiely, A P" uniqKey="Kiely A">A.P. Kiely</name></author><author><name sortKey="Asi, Y T" uniqKey="Asi Y">Y.T. Asi</name></author><author><name sortKey="Kara, E" uniqKey="Kara E">E. Kara</name></author><author><name sortKey="Limousin, P" uniqKey="Limousin P">P. Limousin</name></author><author><name sortKey="Ling, H" uniqKey="Ling H">H. Ling</name></author><author><name sortKey="Lewis, P" uniqKey="Lewis P">P. Lewis</name></author><author><name sortKey="Proukakis, C" uniqKey="Proukakis C">C. Proukakis</name></author><author><name sortKey="Quinn, N" uniqKey="Quinn N">N. Quinn</name></author><author><name sortKey="Lees, A J" uniqKey="Lees A">A.J. Lees</name></author><author><name sortKey="Hardy, J" uniqKey="Hardy J">J. Hardy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pasanen, P" uniqKey="Pasanen P">P. Pasanen</name></author><author><name sortKey="Myllykangas, L" uniqKey="Myllykangas L">L. Myllykangas</name></author><author><name sortKey="Siitonen, M" uniqKey="Siitonen M">M. Siitonen</name></author><author><name sortKey="Raunio, A" uniqKey="Raunio A">A. Raunio</name></author><author><name sortKey="Kaakkola, S" uniqKey="Kaakkola S">S. Kaakkola</name></author><author><name sortKey="Lyytinen, J" uniqKey="Lyytinen J">J. Lyytinen</name></author><author><name sortKey="Tienari, P J" uniqKey="Tienari P">P.J. Tienari</name></author><author><name sortKey="Poyhonen, M" uniqKey="Poyhonen M">M. Pöyhönen</name></author><author><name sortKey="Paetau, A" uniqKey="Paetau A">A. Paetau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reeve, A" uniqKey="Reeve A">A. Reeve</name></author><author><name sortKey="Simcox, E" uniqKey="Simcox E">E. Simcox</name></author><author><name sortKey="Turnbull, D" uniqKey="Turnbull D">D. Turnbull</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Subramaniam, S R" uniqKey="Subramaniam S">S.R. Subramaniam</name></author><author><name sortKey="Chesselet, M F" uniqKey="Chesselet M">M.F. Chesselet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mosharov, E V" uniqKey="Mosharov E">E.V. Mosharov</name></author><author><name sortKey="Larsen, K E" uniqKey="Larsen K">K.E. Larsen</name></author><author><name sortKey="Kanter, E" uniqKey="Kanter E">E. Kanter</name></author><author><name sortKey="Phillips, K A" uniqKey="Phillips K">K.A. Phillips</name></author><author><name sortKey="Wilson, K" uniqKey="Wilson K">K. Wilson</name></author><author><name sortKey="Schmitz, Y" uniqKey="Schmitz Y">Y. Schmitz</name></author><author><name sortKey="Krantz, D E" uniqKey="Krantz D">D.E. Krantz</name></author><author><name sortKey="Kobayashi, K" uniqKey="Kobayashi K">K. Kobayashi</name></author><author><name sortKey="Edwards, R H" uniqKey="Edwards R">R.H. Edwards</name></author><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mu Oz, P" uniqKey="Mu Oz P">P. Muñoz</name></author><author><name sortKey="Huenchuguala, S" uniqKey="Huenchuguala S">S. Huenchuguala</name></author><author><name sortKey="Paris, I" uniqKey="Paris I">I. Paris</name></author><author><name sortKey="Segura Aguilar, J" uniqKey="Segura Aguilar J">J. Segura-Aguilar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author><author><name sortKey="Mosharov, E" uniqKey="Mosharov E">E. Mosharov</name></author><author><name sortKey="Talloczy, Z" uniqKey="Talloczy Z">Z. Talloczy</name></author><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Simon, J D" uniqKey="Simon J">J.D. Simon</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xuan, Q" uniqKey="Xuan Q">Q. Xuan</name></author><author><name sortKey="Xu, S L" uniqKey="Xu S">S.L. Xu</name></author><author><name sortKey="Lu, D H" uniqKey="Lu D">D.H. Lu</name></author><author><name sortKey="Yu, S" uniqKey="Yu S">S. Yu</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M. Zhou</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Uéda</name></author><author><name sortKey="Cui, Y Q" uniqKey="Cui Y">Y.Q. Cui</name></author><author><name sortKey="Zhang, B Y" uniqKey="Zhang B">B.Y. Zhang</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Phillips, K" uniqKey="Phillips K">K. Phillips</name></author><author><name sortKey="Wielgus, A R" uniqKey="Wielgus A">A.R. Wielgus</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="Albertini, A" uniqKey="Albertini A">A. Albertini</name></author><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Faust, R" uniqKey="Faust R">R. Faust</name></author><author><name sortKey="Qian, S Y" uniqKey="Qian S">S.Y. Qian</name></author><author><name sortKey="Miller, D S" uniqKey="Miller D">D.S. Miller</name></author><author><name sortKey="Chignell, C F" uniqKey="Chignell C">C.F. Chignell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chartier Harlin, M C" uniqKey="Chartier Harlin M">M.C. Chartier-Harlin</name></author><author><name sortKey="Kachergus, J" uniqKey="Kachergus J">J. Kachergus</name></author><author><name sortKey="Roumier, C" uniqKey="Roumier C">C. Roumier</name></author><author><name sortKey="Mouroux, V" uniqKey="Mouroux V">V. Mouroux</name></author><author><name sortKey="Douay, X" uniqKey="Douay X">X. Douay</name></author><author><name sortKey="Lincoln, S" uniqKey="Lincoln S">S. Lincoln</name></author><author><name sortKey="Levecque, C" uniqKey="Levecque C">C. Levecque</name></author><author><name sortKey="Larvor, L" uniqKey="Larvor L">L. Larvor</name></author><author><name sortKey="Andrieux, J" uniqKey="Andrieux J">J. Andrieux</name></author><author><name sortKey="Hulihan, M" uniqKey="Hulihan M">M. Hulihan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byers, B" uniqKey="Byers B">B. Byers</name></author><author><name sortKey="Cord, B" uniqKey="Cord B">B. Cord</name></author><author><name sortKey="Nguyen, H N" uniqKey="Nguyen H">H.N. Nguyen</name></author><author><name sortKey="Schule, B" uniqKey="Schule B">B. Schüle</name></author><author><name sortKey="Fenno, L" uniqKey="Fenno L">L. Fenno</name></author><author><name sortKey="Lee, P C" uniqKey="Lee P">P.C. Lee</name></author><author><name sortKey="Deisseroth, K" uniqKey="Deisseroth K">K. Deisseroth</name></author><author><name sortKey="Langston, J W" uniqKey="Langston J">J.W. Langston</name></author><author><name sortKey="Pera, R R" uniqKey="Pera R">R.R. Pera</name></author><author><name sortKey="Palmer, T D" uniqKey="Palmer T">T.D. Palmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanda, S" uniqKey="Kanda S">S. Kanda</name></author><author><name sortKey="Bishop, J F" uniqKey="Bishop J">J.F. Bishop</name></author><author><name sortKey="Eglitis, M A" uniqKey="Eglitis M">M.A. Eglitis</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Mouradian, M M" uniqKey="Mouradian M">M.M. Mouradian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narhi, L" uniqKey="Narhi L">L. Narhi</name></author><author><name sortKey="Wood, S J" uniqKey="Wood S">S.J. Wood</name></author><author><name sortKey="Steavenson, S" uniqKey="Steavenson S">S. Steavenson</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Wu, G M" uniqKey="Wu G">G.M. Wu</name></author><author><name sortKey="Anafi, D" uniqKey="Anafi D">D. Anafi</name></author><author><name sortKey="Kaufman, S A" uniqKey="Kaufman S">S.A. Kaufman</name></author><author><name sortKey="Martin, F" uniqKey="Martin F">F. Martin</name></author><author><name sortKey="Sitney, K" uniqKey="Sitney K">K. Sitney</name></author><author><name sortKey="Denis, P" uniqKey="Denis P">P. Denis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khalaf, O" uniqKey="Khalaf O">O. Khalaf</name></author><author><name sortKey="Fauvet, B" uniqKey="Fauvet B">B. Fauvet</name></author><author><name sortKey="Oueslati, A" uniqKey="Oueslati A">A. Oueslati</name></author><author><name sortKey="Dikiy, I" uniqKey="Dikiy I">I. Dikiy</name></author><author><name sortKey="Mahul Mellier, A L" uniqKey="Mahul Mellier A">A.L. Mahul-Mellier</name></author><author><name sortKey="Ruggeri, F S" uniqKey="Ruggeri F">F.S. Ruggeri</name></author><author><name sortKey="Mbefo, M" uniqKey="Mbefo M">M. Mbefo</name></author><author><name sortKey="Vercruysse, F" uniqKey="Vercruysse F">F. Vercruysse</name></author><author><name sortKey="Dietler, G" uniqKey="Dietler G">G. Dietler</name></author><author><name sortKey="Lee, S J" uniqKey="Lee S">S.J. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rutherford, N J" uniqKey="Rutherford N">N.J. Rutherford</name></author><author><name sortKey="Moore, B D" uniqKey="Moore B">B.D. Moore</name></author><author><name sortKey="Golde, T E" uniqKey="Golde T">T.E. Golde</name></author><author><name sortKey="Giasson, B I" uniqKey="Giasson B">B.I. Giasson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghosh, D" uniqKey="Ghosh D">D. Ghosh</name></author><author><name sortKey="Sahay, S" uniqKey="Sahay S">S. Sahay</name></author><author><name sortKey="Ranjan, P" uniqKey="Ranjan P">P. Ranjan</name></author><author><name sortKey="Salot, S" uniqKey="Salot S">S. Salot</name></author><author><name sortKey="Mohite, G M" uniqKey="Mohite G">G.M. Mohite</name></author><author><name sortKey="Singh, P K" uniqKey="Singh P">P.K. Singh</name></author><author><name sortKey="Dwivedi, S" uniqKey="Dwivedi S">S. Dwivedi</name></author><author><name sortKey="Carvalho, E" uniqKey="Carvalho E">E. Carvalho</name></author><author><name sortKey="Banerjee, R" uniqKey="Banerjee R">R. Banerjee</name></author><author><name sortKey="Kumar, A" uniqKey="Kumar A">A. Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yan, J Q" uniqKey="Yan J">J.Q. Yan</name></author><author><name sortKey="Yuan, Y H" uniqKey="Yuan Y">Y.H. Yuan</name></author><author><name sortKey="Gao, Y N" uniqKey="Gao Y">Y.N. Gao</name></author><author><name sortKey="Huang, J Y" uniqKey="Huang J">J.Y. Huang</name></author><author><name sortKey="Ma, K L" uniqKey="Ma K">K.L. Ma</name></author><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y. Gao</name></author><author><name sortKey="Zhang, W Q" uniqKey="Zhang W">W.Q. Zhang</name></author><author><name sortKey="Guo, X F" uniqKey="Guo X">X.F. Guo</name></author><author><name sortKey="Chen, N H" uniqKey="Chen N">N.H. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ramanan, V K" uniqKey="Ramanan V">V.K. Ramanan</name></author><author><name sortKey="Saykin, A J" uniqKey="Saykin A">A.J. Saykin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satake, W" uniqKey="Satake W">W. Satake</name></author><author><name sortKey="Nakabayashi, Y" uniqKey="Nakabayashi Y">Y. Nakabayashi</name></author><author><name sortKey="Mizuta, I" uniqKey="Mizuta I">I. Mizuta</name></author><author><name sortKey="Hirota, Y" uniqKey="Hirota Y">Y. Hirota</name></author><author><name sortKey="Ito, C" uniqKey="Ito C">C. Ito</name></author><author><name sortKey="Kubo, M" uniqKey="Kubo M">M. Kubo</name></author><author><name sortKey="Kawaguchi, T" uniqKey="Kawaguchi T">T. Kawaguchi</name></author><author><name sortKey="Tsunoda, T" uniqKey="Tsunoda T">T. Tsunoda</name></author><author><name sortKey="Watanabe, M" uniqKey="Watanabe M">M. Watanabe</name></author><author><name sortKey="Takeda, A" uniqKey="Takeda A">A. Takeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spillantini, M G" uniqKey="Spillantini M">M.G. Spillantini</name></author><author><name sortKey="Schmidt, M L" uniqKey="Schmidt M">M.L. Schmidt</name></author><author><name sortKey="Lee, V M" uniqKey="Lee V">V.M. Lee</name></author><author><name sortKey="Trojanowski, J Q" uniqKey="Trojanowski J">J.Q. Trojanowski</name></author><author><name sortKey="Jakes, R" uniqKey="Jakes R">R. Jakes</name></author><author><name sortKey="Goedert, M" uniqKey="Goedert M">M. Goedert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, N Y" uniqKey="Zhang N">N.Y. Zhang</name></author><author><name sortKey="Tang, Z" uniqKey="Tang Z">Z. Tang</name></author><author><name sortKey="Liu, C W" uniqKey="Liu C">C.W. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lashuel, H A" uniqKey="Lashuel H">H.A. Lashuel</name></author><author><name sortKey="Grillo Bosch, D" uniqKey="Grillo Bosch D">D. Grillo-Bosch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cole, N B" uniqKey="Cole N">N.B. Cole</name></author><author><name sortKey="Murphy, D D" uniqKey="Murphy D">D.D. Murphy</name></author><author><name sortKey="Lebowitz, J" uniqKey="Lebowitz J">J. Lebowitz</name></author><author><name sortKey="Di Noto, L" uniqKey="Di Noto L">L. Di Noto</name></author><author><name sortKey="Levine, R L" uniqKey="Levine R">R.L. Levine</name></author><author><name sortKey="Nussbaum, R L" uniqKey="Nussbaum R">R.L. Nussbaum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wakabayashi, K" uniqKey="Wakabayashi K">K. Wakabayashi</name></author><author><name sortKey="Tanji, K" uniqKey="Tanji K">K. Tanji</name></author><author><name sortKey="Mori, F" uniqKey="Mori F">F. Mori</name></author><author><name sortKey="Takahashi, H" uniqKey="Takahashi H">H. Takahashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fagerqvist, T" uniqKey="Fagerqvist T">T. Fagerqvist</name></author><author><name sortKey="Lindstrom, V" uniqKey="Lindstrom V">V. Lindström</name></author><author><name sortKey="Nordstrom, E" uniqKey="Nordstrom E">E. Nordström</name></author><author><name sortKey="Lord, A" uniqKey="Lord A">A. Lord</name></author><author><name sortKey="Tucker, S M" uniqKey="Tucker S">S.M. Tucker</name></author><author><name sortKey="Su, X" uniqKey="Su X">X. Su</name></author><author><name sortKey="Sahlin, C" uniqKey="Sahlin C">C. Sahlin</name></author><author><name sortKey="Kasrayan, A" uniqKey="Kasrayan A">A. Kasrayan</name></author><author><name sortKey="Andersson, J" uniqKey="Andersson J">J. Andersson</name></author><author><name sortKey="Welander, H" uniqKey="Welander H">H. Welander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, H J" uniqKey="Lee H">H.J. Lee</name></author><author><name sortKey="Lee, S J" uniqKey="Lee S">S.J. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lindstrom, V" uniqKey="Lindstrom V">V. Lindström</name></author><author><name sortKey="Fagerqvist, T" uniqKey="Fagerqvist T">T. Fagerqvist</name></author><author><name sortKey="Nordstrom, E" uniqKey="Nordstrom E">E. Nordström</name></author><author><name sortKey="Eriksson, F" uniqKey="Eriksson F">F. Eriksson</name></author><author><name sortKey="Lord, A" uniqKey="Lord A">A. Lord</name></author><author><name sortKey="Tucker, S" uniqKey="Tucker S">S. Tucker</name></author><author><name sortKey="Andersson, J" uniqKey="Andersson J">J. Andersson</name></author><author><name sortKey="Johannesson, M" uniqKey="Johannesson M">M. Johannesson</name></author><author><name sortKey="Schell, H" uniqKey="Schell H">H. Schell</name></author><author><name sortKey="Kahle, P J" uniqKey="Kahle P">P.J. Kahle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lavedan, C" uniqKey="Lavedan C">C. Lavedan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maroteaux, L" uniqKey="Maroteaux L">L. Maroteaux</name></author><author><name sortKey="Campanelli, J T" uniqKey="Campanelli J">J.T. Campanelli</name></author><author><name sortKey="Scheller, R H" uniqKey="Scheller R">R.H. Scheller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bendor, J T" uniqKey="Bendor J">J.T. Bendor</name></author><author><name sortKey="Logan, T P" uniqKey="Logan T">T.P. Logan</name></author><author><name sortKey="Edwards, R H" uniqKey="Edwards R">R.H. Edwards</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="George, J M" uniqKey="George J">J.M. George</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bartels, T" uniqKey="Bartels T">T. Bartels</name></author><author><name sortKey="Choi, J G" uniqKey="Choi J">J.G. Choi</name></author><author><name sortKey="Selkoe, D J" uniqKey="Selkoe D">D.J. Selkoe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, W" uniqKey="Wang W">W. Wang</name></author><author><name sortKey="Perovic, I" uniqKey="Perovic I">I. Perovic</name></author><author><name sortKey="Chittuluru, J" uniqKey="Chittuluru J">J. Chittuluru</name></author><author><name sortKey="Kaganovich, A" uniqKey="Kaganovich A">A. Kaganovich</name></author><author><name sortKey="Nguyen, L T" uniqKey="Nguyen L">L.T. Nguyen</name></author><author><name sortKey="Liao, J" uniqKey="Liao J">J. Liao</name></author><author><name sortKey="Auclair, J R" uniqKey="Auclair J">J.R. Auclair</name></author><author><name sortKey="Johnson, D" uniqKey="Johnson D">D. Johnson</name></author><author><name sortKey="Landeru, A" uniqKey="Landeru A">A. Landeru</name></author><author><name sortKey="Simorellis, A K" uniqKey="Simorellis A">A.K. Simorellis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Conway, K A" uniqKey="Conway K">K.A. Conway</name></author><author><name sortKey="Lee, S J" uniqKey="Lee S">S.J. Lee</name></author><author><name sortKey="Rochet, J C" uniqKey="Rochet J">J.C. Rochet</name></author><author><name sortKey="Ding, T T" uniqKey="Ding T">T.T. Ding</name></author><author><name sortKey="Harper, J D" uniqKey="Harper J">J.D. Harper</name></author><author><name sortKey="Williamson, R E" uniqKey="Williamson R">R.E. Williamson</name></author><author><name sortKey="Lansbury, P T" uniqKey="Lansbury P">P.T. Lansbury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Conway, K A" uniqKey="Conway K">K.A. Conway</name></author><author><name sortKey="Rochet, J C" uniqKey="Rochet J">J.C. Rochet</name></author><author><name sortKey="Bieganski, R M" uniqKey="Bieganski R">R.M. Bieganski</name></author><author><name sortKey="Lansbury, P T" uniqKey="Lansbury P">P.T. Lansbury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fujiwara, H" uniqKey="Fujiwara H">H. Fujiwara</name></author><author><name sortKey="Hasegawa, M" uniqKey="Hasegawa M">M. Hasegawa</name></author><author><name sortKey="Dohmae, N" uniqKey="Dohmae N">N. Dohmae</name></author><author><name sortKey="Kawashima, A" uniqKey="Kawashima A">A. Kawashima</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E. Masliah</name></author><author><name sortKey="Goldberg, M S" uniqKey="Goldberg M">M.S. Goldberg</name></author><author><name sortKey="Shen, J" uniqKey="Shen J">J. Shen</name></author><author><name sortKey="Takio, K" uniqKey="Takio K">K. Takio</name></author><author><name sortKey="Iwatsubo, T" uniqKey="Iwatsubo T">T. Iwatsubo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jethva, P N" uniqKey="Jethva P">P.N. Jethva</name></author><author><name sortKey="Kardani, J R" uniqKey="Kardani J">J.R. Kardani</name></author><author><name sortKey="Roy, I" uniqKey="Roy I">I. Roy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jenco, J M" uniqKey="Jenco J">J.M. Jenco</name></author><author><name sortKey="Rawlingson, A" uniqKey="Rawlingson A">A. Rawlingson</name></author><author><name sortKey="Daniels, B" uniqKey="Daniels B">B. Daniels</name></author><author><name sortKey="Morris, A J" uniqKey="Morris A">A.J. Morris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murphy, D D" uniqKey="Murphy D">D.D. Murphy</name></author><author><name sortKey="Rueter, S M" uniqKey="Rueter S">S.M. Rueter</name></author><author><name sortKey="Trojanowski, J Q" uniqKey="Trojanowski J">J.Q. Trojanowski</name></author><author><name sortKey="Lee, V M" uniqKey="Lee V">V.M. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cabin, D E" uniqKey="Cabin D">D.E. Cabin</name></author><author><name sortKey="Shimazu, K" uniqKey="Shimazu K">K. Shimazu</name></author><author><name sortKey="Murphy, D" uniqKey="Murphy D">D. Murphy</name></author><author><name sortKey="Cole, N B" uniqKey="Cole N">N.B. Cole</name></author><author><name sortKey="Gottschalk, W" uniqKey="Gottschalk W">W. Gottschalk</name></author><author><name sortKey="Mcilwain, K L" uniqKey="Mcilwain K">K.L. McIlwain</name></author><author><name sortKey="Orrison, B" uniqKey="Orrison B">B. Orrison</name></author><author><name sortKey="Chen, A" uniqKey="Chen A">A. Chen</name></author><author><name sortKey="Ellis, C E" uniqKey="Ellis C">C.E. Ellis</name></author><author><name sortKey="Paylor, R" uniqKey="Paylor R">R. Paylor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chandra, S" uniqKey="Chandra S">S. Chandra</name></author><author><name sortKey="Fornai, F" uniqKey="Fornai F">F. Fornai</name></author><author><name sortKey="Kwon, H B" uniqKey="Kwon H">H.B. Kwon</name></author><author><name sortKey="Yazdani, U" uniqKey="Yazdani U">U. Yazdani</name></author><author><name sortKey="Atasoy, D" uniqKey="Atasoy D">D. Atasoy</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X. Liu</name></author><author><name sortKey="Hammer, R E" uniqKey="Hammer R">R.E. Hammer</name></author><author><name sortKey="Battaglia, G" uniqKey="Battaglia G">G. Battaglia</name></author><author><name sortKey="German, D C" uniqKey="German D">D.C. German</name></author><author><name sortKey="Castillo, P E" uniqKey="Castillo P">P.E. Castillo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, R H" uniqKey="Chen R">R.H. Chen</name></author><author><name sortKey="Wislet Gendebien, S" uniqKey="Wislet Gendebien S">S. Wislet-Gendebien</name></author><author><name sortKey="Samuel, F" uniqKey="Samuel F">F. Samuel</name></author><author><name sortKey="Visanji, N P" uniqKey="Visanji N">N.P. Visanji</name></author><author><name sortKey="Zhang, G" uniqKey="Zhang G">G. Zhang</name></author><author><name sortKey="Marsilio, D" uniqKey="Marsilio D">D. Marsilio</name></author><author><name sortKey="Langman, T" uniqKey="Langman T">T. Langman</name></author><author><name sortKey="Fraser, P E" uniqKey="Fraser P">P.E. Fraser</name></author><author><name sortKey="Tandon, A" uniqKey="Tandon A">A. Tandon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin, L J" uniqKey="Martin L">L.J. Martin</name></author><author><name sortKey="Pan, Y" uniqKey="Pan Y">Y. Pan</name></author><author><name sortKey="Price, A C" uniqKey="Price A">A.C. Price</name></author><author><name sortKey="Sterling, W" uniqKey="Sterling W">W. Sterling</name></author><author><name sortKey="Copeland, N G" uniqKey="Copeland N">N.G. Copeland</name></author><author><name sortKey="Jenkins, N A" uniqKey="Jenkins N">N.A. Jenkins</name></author><author><name sortKey="Price, D L" uniqKey="Price D">D.L. Price</name></author><author><name sortKey="Lee, M K" uniqKey="Lee M">M.K. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Devi, L" uniqKey="Devi L">L. Devi</name></author><author><name sortKey="Raghavendran, V" uniqKey="Raghavendran V">V. Raghavendran</name></author><author><name sortKey="Prabhu, B M" uniqKey="Prabhu B">B.M. Prabhu</name></author><author><name sortKey="Avadhani, N G" uniqKey="Avadhani N">N.G. Avadhani</name></author><author><name sortKey="Anandatheerthavarada, H K" uniqKey="Anandatheerthavarada H">H.K. Anandatheerthavarada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, G" uniqKey="Liu G">G. Liu</name></author><author><name sortKey="Zhang, C" uniqKey="Zhang C">C. Zhang</name></author><author><name sortKey="Yin, J" uniqKey="Yin J">J. Yin</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Cheng, F" uniqKey="Cheng F">F. Cheng</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Uéda</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author><author><name sortKey="Yu, S" uniqKey="Yu S">S. Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chinta, S J" uniqKey="Chinta S">S.J. Chinta</name></author><author><name sortKey="Mallajosyula, J K" uniqKey="Mallajosyula J">J.K. Mallajosyula</name></author><author><name sortKey="Rane, A" uniqKey="Rane A">A. Rane</name></author><author><name sortKey="Andersen, J K" uniqKey="Andersen J">J.K. Andersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakamura, K" uniqKey="Nakamura K">K. Nakamura</name></author><author><name sortKey="Nemani, V M" uniqKey="Nemani V">V.M. Nemani</name></author><author><name sortKey="Azarbal, F" uniqKey="Azarbal F">F. Azarbal</name></author><author><name sortKey="Skibinski, G" uniqKey="Skibinski G">G. Skibinski</name></author><author><name sortKey="Levy, J M" uniqKey="Levy J">J.M. Levy</name></author><author><name sortKey="Egami, K" uniqKey="Egami K">K. Egami</name></author><author><name sortKey="Munishkina, L" uniqKey="Munishkina L">L. Munishkina</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Gardner, B" uniqKey="Gardner B">B. Gardner</name></author><author><name sortKey="Wakabayashi, J" uniqKey="Wakabayashi J">J. Wakabayashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cooper, A A" uniqKey="Cooper A">A.A. Cooper</name></author><author><name sortKey="Gitler, A D" uniqKey="Gitler A">A.D. Gitler</name></author><author><name sortKey="Cashikar, A" uniqKey="Cashikar A">A. Cashikar</name></author><author><name sortKey="Haynes, C M" uniqKey="Haynes C">C.M. Haynes</name></author><author><name sortKey="Hill, K J" uniqKey="Hill K">K.J. Hill</name></author><author><name sortKey="Bhullar, B" uniqKey="Bhullar B">B. Bhullar</name></author><author><name sortKey="Liu, K" uniqKey="Liu K">K. Liu</name></author><author><name sortKey="Xu, K" uniqKey="Xu K">K. Xu</name></author><author><name sortKey="Strathearn, K E" uniqKey="Strathearn K">K.E. Strathearn</name></author><author><name sortKey="Liu, F" uniqKey="Liu F">F. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gitler, A D" uniqKey="Gitler A">A.D. Gitler</name></author><author><name sortKey="Bevis, B J" uniqKey="Bevis B">B.J. Bevis</name></author><author><name sortKey="Shorter, J" uniqKey="Shorter J">J. Shorter</name></author><author><name sortKey="Strathearn, K E" uniqKey="Strathearn K">K.E. Strathearn</name></author><author><name sortKey="Hamamichi, S" uniqKey="Hamamichi S">S. Hamamichi</name></author><author><name sortKey="Su, L J" uniqKey="Su L">L.J. Su</name></author><author><name sortKey="Caldwell, K A" uniqKey="Caldwell K">K.A. Caldwell</name></author><author><name sortKey="Caldwell, G A" uniqKey="Caldwell G">G.A. Caldwell</name></author><author><name sortKey="Rochet, J C" uniqKey="Rochet J">J.C. Rochet</name></author><author><name sortKey="Mccaffery, J M" uniqKey="Mccaffery J">J.M. McCaffery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thayanidhi, N" uniqKey="Thayanidhi N">N. Thayanidhi</name></author><author><name sortKey="Helm, J R" uniqKey="Helm J">J.R. Helm</name></author><author><name sortKey="Nycz, D C" uniqKey="Nycz D">D.C. Nycz</name></author><author><name sortKey="Bentley, M" uniqKey="Bentley M">M. Bentley</name></author><author><name sortKey="Liang, Y" uniqKey="Liang Y">Y. Liang</name></author><author><name sortKey="Hay, J C" uniqKey="Hay J">J.C. Hay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ebrahimi Fakhari, D" uniqKey="Ebrahimi Fakhari D">D. Ebrahimi-Fakhari</name></author><author><name sortKey="Cantuti Castelvetri, I" uniqKey="Cantuti Castelvetri I">I. Cantuti-Castelvetri</name></author><author><name sortKey="Fan, Z" uniqKey="Fan Z">Z. Fan</name></author><author><name sortKey="Rockenstein, E" uniqKey="Rockenstein E">E. Rockenstein</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E. Masliah</name></author><author><name sortKey="Hyman, B T" uniqKey="Hyman B">B.T. Hyman</name></author><author><name sortKey="Mclean, P J" uniqKey="Mclean P">P.J. McLean</name></author><author><name sortKey="Unni, V K" uniqKey="Unni V">V.K. Unni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Volles, M J" uniqKey="Volles M">M.J. Volles</name></author><author><name sortKey="Lee, S J" uniqKey="Lee S">S.J. Lee</name></author><author><name sortKey="Rochet, J C" uniqKey="Rochet J">J.C. Rochet</name></author><author><name sortKey="Shtilerman, M D" uniqKey="Shtilerman M">M.D. Shtilerman</name></author><author><name sortKey="Ding, T T" uniqKey="Ding T">T.T. Ding</name></author><author><name sortKey="Kessler, J C" uniqKey="Kessler J">J.C. Kessler</name></author><author><name sortKey="Lansbury, P T" uniqKey="Lansbury P">P.T. Lansbury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dias, V" uniqKey="Dias V">V. Dias</name></author><author><name sortKey="Junn, E" uniqKey="Junn E">E. Junn</name></author><author><name sortKey="Mouradian, M M" uniqKey="Mouradian M">M.M. Mouradian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oueslati, A" uniqKey="Oueslati A">A. Oueslati</name></author><author><name sortKey="Ximerakis, M" uniqKey="Ximerakis M">M. Ximerakis</name></author><author><name sortKey="Vekrellis, K" uniqKey="Vekrellis K">K. Vekrellis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Surgucheva, I" uniqKey="Surgucheva I">I. Surgucheva</name></author><author><name sortKey="Newell, K L" uniqKey="Newell K">K.L. Newell</name></author><author><name sortKey="Burns, J" uniqKey="Burns J">J. Burns</name></author><author><name sortKey="Surguchov, A" uniqKey="Surguchov A">A. Surguchov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anderson, J P" uniqKey="Anderson J">J.P. Anderson</name></author><author><name sortKey="Walker, D E" uniqKey="Walker D">D.E. Walker</name></author><author><name sortKey="Goldstein, J M" uniqKey="Goldstein J">J.M. Goldstein</name></author><author><name sortKey="De Laat, R" uniqKey="De Laat R">R. de Laat</name></author><author><name sortKey="Banducci, K" uniqKey="Banducci K">K. Banducci</name></author><author><name sortKey="Caccavello, R J" uniqKey="Caccavello R">R.J. Caccavello</name></author><author><name sortKey="Barbour, R" uniqKey="Barbour R">R. Barbour</name></author><author><name sortKey="Huang, J" uniqKey="Huang J">J. Huang</name></author><author><name sortKey="Kling, K" uniqKey="Kling K">K. Kling</name></author><author><name sortKey="Lee, M" uniqKey="Lee M">M. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kahle, P J" uniqKey="Kahle P">P.J. Kahle</name></author><author><name sortKey="Neumann, M" uniqKey="Neumann M">M. Neumann</name></author><author><name sortKey="Ozmen, L" uniqKey="Ozmen L">L. Ozmen</name></author><author><name sortKey="Muller, V" uniqKey="Muller V">V. Muller</name></author><author><name sortKey="Jacobsen, H" uniqKey="Jacobsen H">H. Jacobsen</name></author><author><name sortKey="Schindzielorz, A" uniqKey="Schindzielorz A">A. Schindzielorz</name></author><author><name sortKey="Okochi, M" uniqKey="Okochi M">M. Okochi</name></author><author><name sortKey="Leimer, U" uniqKey="Leimer U">U. Leimer</name></author><author><name sortKey="Van Der Putten, H" uniqKey="Van Der Putten H">H. van der Putten</name></author><author><name sortKey="Probst, A" uniqKey="Probst A">A. Probst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, T" uniqKey="Takahashi T">T. Takahashi</name></author><author><name sortKey="Yamashita, H" uniqKey="Yamashita H">H. Yamashita</name></author><author><name sortKey="Nagano, Y" uniqKey="Nagano Y">Y. Nagano</name></author><author><name sortKey="Nakamura, T" uniqKey="Nakamura T">T. Nakamura</name></author><author><name sortKey="Ohmori, H" uniqKey="Ohmori H">H. Ohmori</name></author><author><name sortKey="Avraham, H" uniqKey="Avraham H">H. Avraham</name></author><author><name sortKey="Avraham, S" uniqKey="Avraham S">S. Avraham</name></author><author><name sortKey="Yasuda, M" uniqKey="Yasuda M">M. Yasuda</name></author><author><name sortKey="Matsumoto, M" uniqKey="Matsumoto M">M. Matsumoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azeredo Da Silveira, S" uniqKey="Azeredo Da Silveira S">S. Azeredo da Silveira</name></author><author><name sortKey="Schneider, B L" uniqKey="Schneider B">B.L. Schneider</name></author><author><name sortKey="Cifuentes Diaz, C" uniqKey="Cifuentes Diaz C">C. Cifuentes-Diaz</name></author><author><name sortKey="Sage, D" uniqKey="Sage D">D. Sage</name></author><author><name sortKey="Abbas Terki, T" uniqKey="Abbas Terki T">T. Abbas-Terki</name></author><author><name sortKey="Iwatsubo, T" uniqKey="Iwatsubo T">T. Iwatsubo</name></author><author><name sortKey="Unser, M" uniqKey="Unser M">M. Unser</name></author><author><name sortKey="Aebischer, P" uniqKey="Aebischer P">P. Aebischer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcfarland, N R" uniqKey="Mcfarland N">N.R. McFarland</name></author><author><name sortKey="Fan, Z" uniqKey="Fan Z">Z. Fan</name></author><author><name sortKey="Xu, K" uniqKey="Xu K">K. Xu</name></author><author><name sortKey="Schwarzschild, M A" uniqKey="Schwarzschild M">M.A. Schwarzschild</name></author><author><name sortKey="Feany, M B" uniqKey="Feany M">M.B. Feany</name></author><author><name sortKey="Hyman, B T" uniqKey="Hyman B">B.T. Hyman</name></author><author><name sortKey="Mclean, P J" uniqKey="Mclean P">P.J. McLean</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sato, H" uniqKey="Sato H">H. Sato</name></author><author><name sortKey="Kato, T" uniqKey="Kato T">T. Kato</name></author><author><name sortKey="Arawaka, S" uniqKey="Arawaka S">S. Arawaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waxman, E A" uniqKey="Waxman E">E.A. Waxman</name></author><author><name sortKey="Giasson, B I" uniqKey="Giasson B">B.I. Giasson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mbefo, M K" uniqKey="Mbefo M">M.K. Mbefo</name></author><author><name sortKey="Paleologou, K E" uniqKey="Paleologou K">K.E. Paleologou</name></author><author><name sortKey="Boucharaba, A" uniqKey="Boucharaba A">A. Boucharaba</name></author><author><name sortKey="Oueslati, A" uniqKey="Oueslati A">A. Oueslati</name></author><author><name sortKey="Schell, H" uniqKey="Schell H">H. Schell</name></author><author><name sortKey="Fournier, M" uniqKey="Fournier M">M. Fournier</name></author><author><name sortKey="Olschewski, D" uniqKey="Olschewski D">D. Olschewski</name></author><author><name sortKey="Yin, G" uniqKey="Yin G">G. Yin</name></author><author><name sortKey="Zweckstetter, M" uniqKey="Zweckstetter M">M. Zweckstetter</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E. Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waxman, E A" uniqKey="Waxman E">E.A. Waxman</name></author><author><name sortKey="Giasson, B I" uniqKey="Giasson B">B.I. Giasson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tenreiro, S" uniqKey="Tenreiro S">S. Tenreiro</name></author><author><name sortKey="Eckermann, K" uniqKey="Eckermann K">K. Eckermann</name></author><author><name sortKey="Outeiro, T F" uniqKey="Outeiro T">T.F. Outeiro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oueslati, A" uniqKey="Oueslati A">A. Oueslati</name></author><author><name sortKey="Schneider, B L" uniqKey="Schneider B">B.L. Schneider</name></author><author><name sortKey="Aebischer, P" uniqKey="Aebischer P">P. Aebischer</name></author><author><name sortKey="Lashuel, H A" uniqKey="Lashuel H">H.A. Lashuel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rott, R" uniqKey="Rott R">R. Rott</name></author><author><name sortKey="Szargel, R" uniqKey="Szargel R">R. Szargel</name></author><author><name sortKey="Shani, V" uniqKey="Shani V">V. Shani</name></author><author><name sortKey="Bisharat, S" uniqKey="Bisharat S">S. Bisharat</name></author><author><name sortKey="Engelender, S" uniqKey="Engelender S">S. Engelender</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haj Yahya, M" uniqKey="Haj Yahya M">M. Haj-Yahya</name></author><author><name sortKey="Fauvet, B" uniqKey="Fauvet B">B. Fauvet</name></author><author><name sortKey="Herman Bachinsky, Y" uniqKey="Herman Bachinsky Y">Y. Herman-Bachinsky</name></author><author><name sortKey="Hejjaoui, M" uniqKey="Hejjaoui M">M. Hejjaoui</name></author><author><name sortKey="Bavikar, S N" uniqKey="Bavikar S">S.N. Bavikar</name></author><author><name sortKey="Karthikeyan, S V" uniqKey="Karthikeyan S">S.V. Karthikeyan</name></author><author><name sortKey="Ciechanover, A" uniqKey="Ciechanover A">A. Ciechanover</name></author><author><name sortKey="Lashuel, H A" uniqKey="Lashuel H">H.A. Lashuel</name></author><author><name sortKey="Brik, A" uniqKey="Brik A">A. Brik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tofaris, G K" uniqKey="Tofaris G">G.K. Tofaris</name></author><author><name sortKey="Garcia Reitbock, P" uniqKey="Garcia Reitbock P">P. Garcia Reitböck</name></author><author><name sortKey="Humby, T" uniqKey="Humby T">T. Humby</name></author><author><name sortKey="Lambourne, S L" uniqKey="Lambourne S">S.L. Lambourne</name></author><author><name sortKey="O Onnell, M" uniqKey="O Onnell M">M. O’Connell</name></author><author><name sortKey="Ghetti, B" uniqKey="Ghetti B">B. Ghetti</name></author><author><name sortKey="Gossage, H" uniqKey="Gossage H">H. Gossage</name></author><author><name sortKey="Emson, P C" uniqKey="Emson P">P.C. Emson</name></author><author><name sortKey="Wilkinson, L S" uniqKey="Wilkinson L">L.S. Wilkinson</name></author><author><name sortKey="Goedert, M" uniqKey="Goedert M">M. Goedert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Souza, J M" uniqKey="Souza J">J.M. Souza</name></author><author><name sortKey="Giasson, B I" uniqKey="Giasson B">B.I. Giasson</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q. Chen</name></author><author><name sortKey="Lee, V M" uniqKey="Lee V">V.M. Lee</name></author><author><name sortKey="Ischiropoulos, H" uniqKey="Ischiropoulos H">H. Ischiropoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vila, M" uniqKey="Vila M">M. Vila</name></author><author><name sortKey="Vukosavic, S" uniqKey="Vukosavic S">S. Vukosavic</name></author><author><name sortKey="Jackson Lewis, V" uniqKey="Jackson Lewis V">V. Jackson-Lewis</name></author><author><name sortKey="Neystat, M" uniqKey="Neystat M">M. Neystat</name></author><author><name sortKey="Jakowec, M" uniqKey="Jakowec M">M. Jakowec</name></author><author><name sortKey="Przedborski, S" uniqKey="Przedborski S">S. Przedborski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hsu, L J" uniqKey="Hsu L">L.J. Hsu</name></author><author><name sortKey="Sagara, Y" uniqKey="Sagara Y">Y. Sagara</name></author><author><name sortKey="Arroyo, A" uniqKey="Arroyo A">A. Arroyo</name></author><author><name sortKey="Rockenstein, E" uniqKey="Rockenstein E">E. Rockenstein</name></author><author><name sortKey="Sisk, A" uniqKey="Sisk A">A. Sisk</name></author><author><name sortKey="Mallory, M" uniqKey="Mallory M">M. Mallory</name></author><author><name sortKey="Wong, J" uniqKey="Wong J">J. Wong</name></author><author><name sortKey="Takenouchi, T" uniqKey="Takenouchi T">T. Takenouchi</name></author><author><name sortKey="Hashimoto, M" uniqKey="Hashimoto M">M. Hashimoto</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E. Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hashimoto, M" uniqKey="Hashimoto M">M. Hashimoto</name></author><author><name sortKey="Takeda, A" uniqKey="Takeda A">A. Takeda</name></author><author><name sortKey="Hsu, L J" uniqKey="Hsu L">L.J. Hsu</name></author><author><name sortKey="Takenouchi, T" uniqKey="Takenouchi T">T. Takenouchi</name></author><author><name sortKey="Masliah, E" uniqKey="Masliah E">E. Masliah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levin, J" uniqKey="Levin J">J. Levin</name></author><author><name sortKey="Hogen, T" uniqKey="Hogen T">T. Högen</name></author><author><name sortKey="Hillmer, A S" uniqKey="Hillmer A">A.S. Hillmer</name></author><author><name sortKey="Bader, B" uniqKey="Bader B">B. Bader</name></author><author><name sortKey="Schmidt, F" uniqKey="Schmidt F">F. Schmidt</name></author><author><name sortKey="Kamp, F" uniqKey="Kamp F">F. Kamp</name></author><author><name sortKey="Kretzschmar, H A" uniqKey="Kretzschmar H">H.A. Kretzschmar</name></author><author><name sortKey="Botzel, K" uniqKey="Botzel K">K. Bötzel</name></author><author><name sortKey="Giese, A" uniqKey="Giese A">A. Giese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, K S" uniqKey="Kim K">K.S. Kim</name></author><author><name sortKey="Choi, S Y" uniqKey="Choi S">S.Y. Choi</name></author><author><name sortKey="Kwon, H Y" uniqKey="Kwon H">H.Y. Kwon</name></author><author><name sortKey="Won, M H" uniqKey="Won M">M.H. Won</name></author><author><name sortKey="Kang, T C" uniqKey="Kang T">T.C. Kang</name></author><author><name sortKey="Kang, J H" uniqKey="Kang J">J.H. Kang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goers, J" uniqKey="Goers J">J. Goers</name></author><author><name sortKey="Manning Bog, A B" uniqKey="Manning Bog A">A.B. Manning-Bog</name></author><author><name sortKey="Mccormack, A L" uniqKey="Mccormack A">A.L. McCormack</name></author><author><name sortKey="Millett, I S" uniqKey="Millett I">I.S. Millett</name></author><author><name sortKey="Doniach, S" uniqKey="Doniach S">S. Doniach</name></author><author><name sortKey="Di Monte, D A" uniqKey="Di Monte D">D.A. di Monte</name></author><author><name sortKey="Uversky, V N" uniqKey="Uversky V">V.N. Uversky</name></author><author><name sortKey="Fink, A L" uniqKey="Fink A">A.L. Fink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, S" uniqKey="Xu S">S. Xu</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M. Zhou</name></author><author><name sortKey="Yu, S" uniqKey="Yu S">S. Yu</name></author><author><name sortKey="Cai, Y" uniqKey="Cai Y">Y. Cai</name></author><author><name sortKey="Zhang, A" uniqKey="Zhang A">A. Zhang</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Uéda</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, M" uniqKey="Zhou M">M. Zhou</name></author><author><name sortKey="Xu, S" uniqKey="Xu S">S. Xu</name></author><author><name sortKey="Mi, J" uniqKey="Mi J">J. Mi</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Uéda</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hasegawa, T" uniqKey="Hasegawa T">T. Hasegawa</name></author><author><name sortKey="Matsuzaki Kobayashi, M" uniqKey="Matsuzaki Kobayashi M">M. Matsuzaki-Kobayashi</name></author><author><name sortKey="Takeda, A" uniqKey="Takeda A">A. Takeda</name></author><author><name sortKey="Sugeno, N" uniqKey="Sugeno N">N. Sugeno</name></author><author><name sortKey="Kikuchi, A" uniqKey="Kikuchi A">A. Kikuchi</name></author><author><name sortKey="Furukawa, K" uniqKey="Furukawa K">K. Furukawa</name></author><author><name sortKey="Perry, G" uniqKey="Perry G">G. Perry</name></author><author><name sortKey="Smith, M A" uniqKey="Smith M">M.A. Smith</name></author><author><name sortKey="Itoyama, Y" uniqKey="Itoyama Y">Y. Itoyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, S" uniqKey="Yu S">S. Yu</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Uéda</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schluter, O M" uniqKey="Schluter O">O.M. Schlüter</name></author><author><name sortKey="Fornai, F" uniqKey="Fornai F">F. Fornai</name></author><author><name sortKey="Alessandri, M G" uniqKey="Alessandri M">M.G. Alessandrí</name></author><author><name sortKey="Takamori, S" uniqKey="Takamori S">S. Takamori</name></author><author><name sortKey="Geppert, M" uniqKey="Geppert M">M. Geppert</name></author><author><name sortKey="Jahn, R" uniqKey="Jahn R">R. Jahn</name></author><author><name sortKey="Sudhof, T C" uniqKey="Sudhof T">T.C. Südhof</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, M" uniqKey="Zhou M">M. Zhou</name></author><author><name sortKey="Xu, S L" uniqKey="Xu S">S.L. Xu</name></author><author><name sortKey="Chen, B" uniqKey="Chen B">B. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomas, B" uniqKey="Thomas B">B. Thomas</name></author><author><name sortKey="Mandir, A S" uniqKey="Mandir A">A.S. Mandir</name></author><author><name sortKey="West, N" uniqKey="West N">N. West</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Andrabi, S A" uniqKey="Andrabi S">S.A. Andrabi</name></author><author><name sortKey="Stirling, W" uniqKey="Stirling W">W. Stirling</name></author><author><name sortKey="Dawson, V L" uniqKey="Dawson V">V.L. Dawson</name></author><author><name sortKey="Dawson, T M" uniqKey="Dawson T">T.M. Dawson</name></author><author><name sortKey="Lee, M K" uniqKey="Lee M">M.K. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klivenyi, P" uniqKey="Klivenyi P">P. Klivenyi</name></author><author><name sortKey="Siwek, D" uniqKey="Siwek D">D. Siwek</name></author><author><name sortKey="Gardian, G" uniqKey="Gardian G">G. Gardian</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L. Yang</name></author><author><name sortKey="Starkov, A" uniqKey="Starkov A">A. Starkov</name></author><author><name sortKey="Cleren, C" uniqKey="Cleren C">C. Cleren</name></author><author><name sortKey="Ferrante, R J" uniqKey="Ferrante R">R.J. Ferrante</name></author><author><name sortKey="Kowall, N W" uniqKey="Kowall N">N.W. Kowall</name></author><author><name sortKey="Abeliovich, A" uniqKey="Abeliovich A">A. Abeliovich</name></author><author><name sortKey="Beal, M F" uniqKey="Beal M">M.F. Beal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Duffy, P E" uniqKey="Duffy P">P.E. Duffy</name></author><author><name sortKey="Tennyson, V M" uniqKey="Tennyson V">V.M. Tennyson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fenichel, G M" uniqKey="Fenichel G">G.M. Fenichel</name></author><author><name sortKey="Bazelon, M" uniqKey="Bazelon M">M. Bazelon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheng, J" uniqKey="Cheng J">J. Cheng</name></author><author><name sortKey="Moss, S C" uniqKey="Moss S">S.C. Moss</name></author><author><name sortKey="Eisner, M" uniqKey="Eisner M">M. Eisner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haavik, J" uniqKey="Haavik J">J. Haavik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okun, M R" uniqKey="Okun M">M.R. Okun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author><author><name sortKey="Bogulavsky, J" uniqKey="Bogulavsky J">J. Bogulavsky</name></author><author><name sortKey="Larsen, K E" uniqKey="Larsen K">K.E. Larsen</name></author><author><name sortKey="Behr, G" uniqKey="Behr G">G. Behr</name></author><author><name sortKey="Karatekin, E" uniqKey="Karatekin E">E. Karatekin</name></author><author><name sortKey="Kleinman, M H" uniqKey="Kleinman M">M.H. Kleinman</name></author><author><name sortKey="Turro, N" uniqKey="Turro N">N. Turro</name></author><author><name sortKey="Krantz, D" uniqKey="Krantz D">D. Krantz</name></author><author><name sortKey="Edwards, R H" uniqKey="Edwards R">R.H. Edwards</name></author><author><name sortKey="Greene, L A" uniqKey="Greene L">L.A. Greene</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="D Mato, R J" uniqKey="D Mato R">R.J. D’Amato</name></author><author><name sortKey="Lipman, Z P" uniqKey="Lipman Z">Z.P. Lipman</name></author><author><name sortKey="Snyder, S H" uniqKey="Snyder S">S.H. Snyder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lindquist, N G" uniqKey="Lindquist N">N.G. Lindquist</name></author><author><name sortKey="Larsson, B S" uniqKey="Larsson B">B.S. Larsson</name></author><author><name sortKey="Lyden Sokolowski, A" uniqKey="Lyden Sokolowski A">A. Lydén-Sokolowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Pietra, R" uniqKey="Pietra R">R. Pietra</name></author><author><name sortKey="Goj, C" uniqKey="Goj C">C. Goj</name></author><author><name sortKey="Mecacci, C" uniqKey="Mecacci C">C. Mecacci</name></author><author><name sortKey="Radice, D" uniqKey="Radice D">D. Radice</name></author><author><name sortKey="Sabbioni, E" uniqKey="Sabbioni E">E. Sabbioni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fornstedt, B" uniqKey="Fornstedt B">B. Fornstedt</name></author><author><name sortKey="Brun, A" uniqKey="Brun A">A. Brun</name></author><author><name sortKey="Rosengren, E" uniqKey="Rosengren E">E. Rosengren</name></author><author><name sortKey="Carlsson, A" uniqKey="Carlsson A">A. Carlsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilczok, T" uniqKey="Wilczok T">T. Wilczok</name></author><author><name sortKey="Stepien, K" uniqKey="Stepien K">K. Stepien</name></author><author><name sortKey="Dzierzega Lecznar, A" uniqKey="Dzierzega Lecznar A">A. Dzierzega-Lecznar</name></author><author><name sortKey="Zajdel, A" uniqKey="Zajdel A">A. Zajdel</name></author><author><name sortKey="Wilczok, A" uniqKey="Wilczok A">A. Wilczok</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shamoto Nagai, M" uniqKey="Shamoto Nagai M">M. Shamoto-Nagai</name></author><author><name sortKey="Maruyama, W" uniqKey="Maruyama W">W. Maruyama</name></author><author><name sortKey="Akao, Y" uniqKey="Akao Y">Y. Akao</name></author><author><name sortKey="Osawa, T" uniqKey="Osawa T">T. Osawa</name></author><author><name sortKey="Tribl, F" uniqKey="Tribl F">F. Tribl</name></author><author><name sortKey="Gerlach, M" uniqKey="Gerlach M">M. Gerlach</name></author><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Riederer, P" uniqKey="Riederer P">P. Riederer</name></author><author><name sortKey="Naoi, M" uniqKey="Naoi M">M. Naoi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zareba, M" uniqKey="Zareba M">M. Zareba</name></author><author><name sortKey="Bober, A" uniqKey="Bober A">A. Bober</name></author><author><name sortKey="Korytowski, W" uniqKey="Korytowski W">W. Korytowski</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Sarna, T" uniqKey="Sarna T">T. Sarna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wakamatsu, K" uniqKey="Wakamatsu K">K. Wakamatsu</name></author><author><name sortKey="Fujikawa, K" uniqKey="Fujikawa K">K. Fujikawa</name></author><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Ito, S" uniqKey="Ito S">S. Ito</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ito, S" uniqKey="Ito S">S. Ito</name></author><author><name sortKey="Wakamatsu, K" uniqKey="Wakamatsu K">K. Wakamatsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Halliday, G M" uniqKey="Halliday G">G.M. Halliday</name></author><author><name sortKey="Ophof, A" uniqKey="Ophof A">A. Ophof</name></author><author><name sortKey="Broe, M" uniqKey="Broe M">M. Broe</name></author><author><name sortKey="Jensen, P H" uniqKey="Jensen P">P.H. Jensen</name></author><author><name sortKey="Kettle, E" uniqKey="Kettle E">E. Kettle</name></author><author><name sortKey="Fedorow, H" uniqKey="Fedorow H">H. Fedorow</name></author><author><name sortKey="Cartwright, M I" uniqKey="Cartwright M">M.I. Cartwright</name></author><author><name sortKey="Griffiths, F M" uniqKey="Griffiths F">F.M. Griffiths</name></author><author><name sortKey="Shepherd, C E" uniqKey="Shepherd C">C.E. Shepherd</name></author><author><name sortKey="Double, K L" uniqKey="Double K">K.L. Double</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Yan, Z F" uniqKey="Yan Z">Z.F. Yan</name></author><author><name sortKey="Gao, J H" uniqKey="Gao J">J.H. Gao</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Huang, X Y" uniqKey="Huang X">X.Y. Huang</name></author><author><name sortKey="Liu, Z" uniqKey="Liu Z">Z. Liu</name></author><author><name sortKey="Yu, S Y" uniqKey="Yu S">S.Y. Yu</name></author><author><name sortKey="Cao, C J" uniqKey="Cao C">C.J. Cao</name></author><author><name sortKey="Zuo, L J" uniqKey="Zuo L">L.J. Zuo</name></author><author><name sortKey="Chen, Z J" uniqKey="Chen Z">Z.J. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilms, H" uniqKey="Wilms H">H. Wilms</name></author><author><name sortKey="Rosenstiel, P" uniqKey="Rosenstiel P">P. Rosenstiel</name></author><author><name sortKey="Sievers, J" uniqKey="Sievers J">J. Sievers</name></author><author><name sortKey="Deuschl, G" uniqKey="Deuschl G">G. Deuschl</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Lucius, R" uniqKey="Lucius R">R. Lucius</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Basso, E" uniqKey="Basso E">E. Basso</name></author><author><name sortKey="Cupaioli, F A" uniqKey="Cupaioli F">F.A. Cupaioli</name></author><author><name sortKey="Ferrari, E" uniqKey="Ferrari E">E. Ferrari</name></author><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author><author><name sortKey="Casella, L" uniqKey="Casella L">L. Casella</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ostergren, A" uniqKey="Ostergren A">A. Ostergren</name></author><author><name sortKey="Annas, A" uniqKey="Annas A">A. Annas</name></author><author><name sortKey="Skog, K" uniqKey="Skog K">K. Skog</name></author><author><name sortKey="Lindquist, N G" uniqKey="Lindquist N">N.G. Lindquist</name></author><author><name sortKey="Brittebo, E B" uniqKey="Brittebo E">E.B. Brittebo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lindquist, N G" uniqKey="Lindquist N">N.G. Lindquist</name></author><author><name sortKey="Larsson, B S" uniqKey="Larsson B">B.S. Larsson</name></author><author><name sortKey="Lyden Sokolowski, A" uniqKey="Lyden Sokolowski A">A. Lyden-Sokolowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Giaveri, G" uniqKey="Giaveri G">G. Giaveri</name></author><author><name sortKey="Gallorini, M" uniqKey="Gallorini M">M. Gallorini</name></author><author><name sortKey="Albertini, A" uniqKey="Albertini A">A. Albertini</name></author><author><name sortKey="Toscani, M" uniqKey="Toscani M">M. Toscani</name></author><author><name sortKey="Pezzoli, G" uniqKey="Pezzoli G">G. Pezzoli</name></author><author><name sortKey="Lucius, R" uniqKey="Lucius R">R. Lucius</name></author><author><name sortKey="Wilms, H" uniqKey="Wilms H">H. Wilms</name></author><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author><author><name sortKey="Ito, S" uniqKey="Ito S">S. Ito</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Mecacci, C" uniqKey="Mecacci C">C. Mecacci</name></author><author><name sortKey="Seraglia, R" uniqKey="Seraglia R">R. Seraglia</name></author><author><name sortKey="Parati, E" uniqKey="Parati E">E. Parati</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Costi, P" uniqKey="Costi P">P. Costi</name></author><author><name sortKey="Mecacci, C" uniqKey="Mecacci C">C. Mecacci</name></author><author><name sortKey="Ito, S" uniqKey="Ito S">S. Ito</name></author><author><name sortKey="Terreni, M" uniqKey="Terreni M">M. Terreni</name></author><author><name sortKey="Sonnino, S" uniqKey="Sonnino S">S. Sonnino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aime, S" uniqKey="Aime S">S. Aime</name></author><author><name sortKey="Fasano, M" uniqKey="Fasano M">M. Fasano</name></author><author><name sortKey="Bergamasco, B" uniqKey="Bergamasco B">B. Bergamasco</name></author><author><name sortKey="Lopiano, L" uniqKey="Lopiano L">L. Lopiano</name></author><author><name sortKey="Valente, G" uniqKey="Valente G">G. Valente</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barden, H" uniqKey="Barden H">H. Barden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Swartz, H M" uniqKey="Swartz H">H.M. Swartz</name></author><author><name sortKey="Sarna, T" uniqKey="Sarna T">T. Sarna</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Bellei, C" uniqKey="Bellei C">C. Bellei</name></author><author><name sortKey="Giannelli, S" uniqKey="Giannelli S">S. Giannelli</name></author><author><name sortKey="Terreni, M R" uniqKey="Terreni M">M.R. Terreni</name></author><author><name sortKey="Gallorini, M" uniqKey="Gallorini M">M. Gallorini</name></author><author><name sortKey="Rizzio, E" uniqKey="Rizzio E">E. Rizzio</name></author><author><name sortKey="Pezzoli, G" uniqKey="Pezzoli G">G. Pezzoli</name></author><author><name sortKey="Albertini, A" uniqKey="Albertini A">A. Albertini</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faucheux, B A" uniqKey="Faucheux B">B.A. Faucheux</name></author><author><name sortKey="Martin, M E" uniqKey="Martin M">M.E. Martin</name></author><author><name sortKey="Beaumont, C" uniqKey="Beaumont C">C. Beaumont</name></author><author><name sortKey="Hauw, J J" uniqKey="Hauw J">J.J. Hauw</name></author><author><name sortKey="Agid, Y" uniqKey="Agid Y">Y. Agid</name></author><author><name sortKey="Hirsch, E C" uniqKey="Hirsch E">E.C. Hirsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Double, K L" uniqKey="Double K">K.L. Double</name></author><author><name sortKey="Gerlach, M" uniqKey="Gerlach M">M. Gerlach</name></author><author><name sortKey="Schunemann, V" uniqKey="Schunemann V">V. Schunemann</name></author><author><name sortKey="Trautwein, A X" uniqKey="Trautwein A">A.X. Trautwein</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Gallorini, M" uniqKey="Gallorini M">M. Gallorini</name></author><author><name sortKey="Youdim, M B" uniqKey="Youdim M">M.B. Youdim</name></author><author><name sortKey="Riederer, P" uniqKey="Riederer P">P. Riederer</name></author><author><name sortKey="Ben Shachar, D" uniqKey="Ben Shachar D">D. Ben-Shachar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ben Shachar, D" uniqKey="Ben Shachar D">D. Ben-Shachar</name></author><author><name sortKey="Riederer, P" uniqKey="Riederer P">P. Riederer</name></author><author><name sortKey="Youdim, M B" uniqKey="Youdim M">M.B. Youdim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grundemann, J" uniqKey="Grundemann J">J. Gründemann</name></author><author><name sortKey="Schlaudraff, F" uniqKey="Schlaudraff F">F. Schlaudraff</name></author><author><name sortKey="Liss, B" uniqKey="Liss B">B. Liss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsuo, Y" uniqKey="Matsuo Y">Y. Matsuo</name></author><author><name sortKey="Kamitani, T" uniqKey="Kamitani T">T. Kamitani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fasano, M" uniqKey="Fasano M">M. Fasano</name></author><author><name sortKey="Giraudo, S" uniqKey="Giraudo S">S. Giraudo</name></author><author><name sortKey="Coha, S" uniqKey="Coha S">S. Coha</name></author><author><name sortKey="Bergamasco, B" uniqKey="Bergamasco B">B. Bergamasco</name></author><author><name sortKey="Lopiano, L" uniqKey="Lopiano L">L. Lopiano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fedorow, H" uniqKey="Fedorow H">H. Fedorow</name></author><author><name sortKey="Halliday, G M" uniqKey="Halliday G">G.M. Halliday</name></author><author><name sortKey="Rickert, C H" uniqKey="Rickert C">C.H. Rickert</name></author><author><name sortKey="Gerlach, M" uniqKey="Gerlach M">M. Gerlach</name></author><author><name sortKey="Riederer, P" uniqKey="Riederer P">P. Riederer</name></author><author><name sortKey="Double, K L" uniqKey="Double K">K.L. Double</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, Y" uniqKey="Chu Y">Y. Chu</name></author><author><name sortKey="Kordower, J H" uniqKey="Kordower J">J.H. Kordower</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Double, K L" uniqKey="Double K">K.L. Double</name></author><author><name sortKey="Ben Shachar, D" uniqKey="Ben Shachar D">D. Ben-Shachar</name></author><author><name sortKey="Youdim, M B" uniqKey="Youdim M">M.B. Youdim</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Riederer, P" uniqKey="Riederer P">P. Riederer</name></author><author><name sortKey="Gerlach, M" uniqKey="Gerlach M">M. Gerlach</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shamoto Nagai, M" uniqKey="Shamoto Nagai M">M. Shamoto-Nagai</name></author><author><name sortKey="Maruyama, W" uniqKey="Maruyama W">W. Maruyama</name></author><author><name sortKey="Yi, H" uniqKey="Yi H">H. Yi</name></author><author><name sortKey="Akao, Y" uniqKey="Akao Y">Y. Akao</name></author><author><name sortKey="Tribl, F" uniqKey="Tribl F">F. Tribl</name></author><author><name sortKey="Gerlach, M" uniqKey="Gerlach M">M. Gerlach</name></author><author><name sortKey="Osawa, T" uniqKey="Osawa T">T. Osawa</name></author><author><name sortKey="Riederer, P" uniqKey="Riederer P">P. Riederer</name></author><author><name sortKey="Naoi, M" uniqKey="Naoi M">M. Naoi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sulzer, D" uniqKey="Sulzer D">D. Sulzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Webb, J L" uniqKey="Webb J">J.L. Webb</name></author><author><name sortKey="Ravikumar, B" uniqKey="Ravikumar B">B. Ravikumar</name></author><author><name sortKey="Atkins, J" uniqKey="Atkins J">J. Atkins</name></author><author><name sortKey="Skepper, J N" uniqKey="Skepper J">J.N. Skepper</name></author><author><name sortKey="Rubinsztein, D C" uniqKey="Rubinsztein D">D.C. Rubinsztein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, T" uniqKey="Pan T">T. Pan</name></author><author><name sortKey="Zhu, J" uniqKey="Zhu J">J. Zhu</name></author><author><name sortKey="Hwu, W J" uniqKey="Hwu W">W.J. Hwu</name></author><author><name sortKey="Jankovic, J" uniqKey="Jankovic J">J. Jankovic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Costi, P" uniqKey="Costi P">P. Costi</name></author><author><name sortKey="Tampellini, D" uniqKey="Tampellini D">D. Tampellini</name></author><author><name sortKey="Gatti, A" uniqKey="Gatti A">A. Gatti</name></author><author><name sortKey="Gerlach, M" uniqKey="Gerlach M">M. Gerlach</name></author><author><name sortKey="Riederer, P" uniqKey="Riederer P">P. Riederer</name></author><author><name sortKey="Fariello, R G" uniqKey="Fariello R">R.G. Fariello</name></author><author><name sortKey="Ito, S" uniqKey="Ito S">S. Ito</name></author><author><name sortKey="Gallorini, M" uniqKey="Gallorini M">M. Gallorini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wakamatsu, K" uniqKey="Wakamatsu K">K. Wakamatsu</name></author><author><name sortKey="Murase, T" uniqKey="Murase T">T. Murase</name></author><author><name sortKey="Zucca, F A" uniqKey="Zucca F">F.A. Zucca</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Ito, S" uniqKey="Ito S">S. Ito</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tessari, I" uniqKey="Tessari I">I. Tessari</name></author><author><name sortKey="Bisaglia, M" uniqKey="Bisaglia M">M. Bisaglia</name></author><author><name sortKey="Valle, F" uniqKey="Valle F">F. Valle</name></author><author><name sortKey="Samori, B" uniqKey="Samori B">B. Samorì</name></author><author><name sortKey="Bergantino, E" uniqKey="Bergantino E">E. Bergantino</name></author><author><name sortKey="Mammi, S" uniqKey="Mammi S">S. Mammi</name></author><author><name sortKey="Bubacco, L" uniqKey="Bubacco L">L. Bubacco</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y H" uniqKey="Li Y">Y.H. Li</name></author><author><name sortKey="Gao, N" uniqKey="Gao N">N. Gao</name></author><author><name sortKey="Ye, Y W" uniqKey="Ye Y">Y.W. Ye</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Yu, S" uniqKey="Yu S">S. Yu</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Uéda</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koo, H J" uniqKey="Koo H">H.J. Koo</name></author><author><name sortKey="Yang, J E" uniqKey="Yang J">J.E. Yang</name></author><author><name sortKey="Park, J H" uniqKey="Park J">J.H. Park</name></author><author><name sortKey="Lee, D" uniqKey="Lee D">D. Lee</name></author><author><name sortKey="Paik, S R" uniqKey="Paik S">S.R. Paik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fornstedt, B" uniqKey="Fornstedt B">B. Fornstedt</name></author><author><name sortKey="Rosengren, E" uniqKey="Rosengren E">E. Rosengren</name></author><author><name sortKey="Carlsson, A" uniqKey="Carlsson A">A. Carlsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liang, C L" uniqKey="Liang C">C.L. Liang</name></author><author><name sortKey="Nelson, O" uniqKey="Nelson O">O. Nelson</name></author><author><name sortKey="Yazdani, U" uniqKey="Yazdani U">U. Yazdani</name></author><author><name sortKey="Pasbakhsh, P" uniqKey="Pasbakhsh P">P. Pasbakhsh</name></author><author><name sortKey="German, D C" uniqKey="German D">D.C. German</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, S" uniqKey="Yu S">S. Yu</name></author><author><name sortKey="Zuo, X" uniqKey="Zuo X">X. Zuo</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Zhang, C" uniqKey="Zhang C">C. Zhang</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M. Zhou</name></author><author><name sortKey="Zhang, Y A" uniqKey="Zhang Y">Y.A. Zhang</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Uéda</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abeliovich, A" uniqKey="Abeliovich A">A. Abeliovich</name></author><author><name sortKey="Schmitz, Y" uniqKey="Schmitz Y">Y. Schmitz</name></author><author><name sortKey="Fari As, I" uniqKey="Fari As I">I. Fariñas</name></author><author><name sortKey="Choi Lundberg, D" uniqKey="Choi Lundberg D">D. Choi-Lundberg</name></author><author><name sortKey="Ho, W H" uniqKey="Ho W">W.H. Ho</name></author><author><name sortKey="Castillo, P E" uniqKey="Castillo P">P.E. Castillo</name></author><author><name sortKey="Shinsky, N" uniqKey="Shinsky N">N. Shinsky</name></author><author><name sortKey="Verdugo, J M" uniqKey="Verdugo J">J.M. Verdugo</name></author><author><name sortKey="Armanini, M" uniqKey="Armanini M">M. Armanini</name></author><author><name sortKey="Ryan, A" uniqKey="Ryan A">A. Ryan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larsen, K E" uniqKey="Larsen K">K.E. Larsen</name></author><author><name sortKey="Schmitz, Y" uniqKey="Schmitz Y">Y. Schmitz</name></author><author><name sortKey="Troyer, M D" uniqKey="Troyer M">M.D. Troyer</name></author><author><name sortKey="Mosharov, E" uniqKey="Mosharov E">E. Mosharov</name></author><author><name sortKey="Dietrich, P" uniqKey="Dietrich P">P. Dietrich</name></author><author><name sortKey="Quazi, A Z" uniqKey="Quazi A">A.Z. Quazi</name></author><author><name sortKey="Savalle, M" uniqKey="Savalle M">M. Savalle</name></author><author><name sortKey="Nemani, V" uniqKey="Nemani V">V. Nemani</name></author><author><name sortKey="Chaudhry, F A" uniqKey="Chaudhry F">F.A. Chaudhry</name></author><author><name sortKey="Edwards, R H" uniqKey="Edwards R">R.H. Edwards</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bellucci, A" uniqKey="Bellucci A">A. Bellucci</name></author><author><name sortKey="Navarria, L" uniqKey="Navarria L">L. Navarria</name></author><author><name sortKey="Falarti, E" uniqKey="Falarti E">E. Falarti</name></author><author><name sortKey="Zaltieri, M" uniqKey="Zaltieri M">M. Zaltieri</name></author><author><name sortKey="Bono, F" uniqKey="Bono F">F. Bono</name></author><author><name sortKey="Collo, G" uniqKey="Collo G">G. Collo</name></author><author><name sortKey="Spillantini, M G" uniqKey="Spillantini M">M.G. Spillantini</name></author><author><name sortKey="Missale, C" uniqKey="Missale C">C. Missale</name></author><author><name sortKey="Spano, P" uniqKey="Spano P">P. Spano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oaks, A W" uniqKey="Oaks A">A.W. Oaks</name></author><author><name sortKey="Marsh Armstrong, N" uniqKey="Marsh Armstrong N">N. Marsh-Armstrong</name></author><author><name sortKey="Jones, J M" uniqKey="Jones J">J.M. Jones</name></author><author><name sortKey="Credle, J J" uniqKey="Credle J">J.J. Credle</name></author><author><name sortKey="Sidhu, A" uniqKey="Sidhu A">A. Sidhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lotharius, J" uniqKey="Lotharius J">J. Lotharius</name></author><author><name sortKey="Brundin, P" uniqKey="Brundin P">P. Brundin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lotharius, J" uniqKey="Lotharius J">J. Lotharius</name></author><author><name sortKey="Barg, S" uniqKey="Barg S">S. Barg</name></author><author><name sortKey="Wiekop, P" uniqKey="Wiekop P">P. Wiekop</name></author><author><name sortKey="Lundberg, C" uniqKey="Lundberg C">C. Lundberg</name></author><author><name sortKey="Raymon, H K" uniqKey="Raymon H">H.K. Raymon</name></author><author><name sortKey="Brundin, P" uniqKey="Brundin P">P. Brundin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mosharov, E V" uniqKey="Mosharov E">E.V. Mosharov</name></author><author><name sortKey="Staal, R G" uniqKey="Staal R">R.G. Staal</name></author><author><name sortKey="Bove, J" uniqKey="Bove J">J. Bove</name></author><author><name sortKey="Prou, D" uniqKey="Prou D">D. Prou</name></author><author><name sortKey="Hananiya, A" uniqKey="Hananiya A">A. Hananiya</name></author><author><name sortKey="Markov, D" uniqKey="Markov D">D. Markov</name></author><author><name sortKey="Poulsen, N" uniqKey="Poulsen N">N. Poulsen</name></author><author><name sortKey="Larsen, K E" uniqKey="Larsen K">K.E. Larsen</name></author><author><name sortKey="Moore, C M" uniqKey="Moore C">C.M. Moore</name></author><author><name sortKey="Troyer, M D" uniqKey="Troyer M">M.D. Troyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, T" uniqKey="Chan T">T. Chan</name></author><author><name sortKey="Chow, A M" uniqKey="Chow A">A.M. Chow</name></author><author><name sortKey="Cheng, X R" uniqKey="Cheng X">X.R. Cheng</name></author><author><name sortKey="Tang, D W" uniqKey="Tang D">D.W. Tang</name></author><author><name sortKey="Brown, I R" uniqKey="Brown I">I.R. Brown</name></author><author><name sortKey="Kerman, K" uniqKey="Kerman K">K. Kerman</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biomolecules</journal-id><journal-id journal-id-type="iso-abbrev">Biomolecules</journal-id><journal-id journal-id-type="publisher-id">biomolecules</journal-id><journal-title-group><journal-title>Biomolecules</journal-title></journal-title-group><issn pub-type="epub">2218-273X</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26057626</article-id><article-id pub-id-type="pmc">4496713</article-id><article-id pub-id-type="doi">10.3390/biom5021122</article-id><article-id pub-id-type="publisher-id">biomolecules-05-01122</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Interaction between Neuromelanin and Alpha-Synuclein in Parkinson’s Disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Shengli</given-names></name><xref ref-type="aff" rid="af1-biomolecules-05-01122">1</xref><xref ref-type="aff" rid="af2-biomolecules-05-01122">2</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Piu</given-names></name><xref ref-type="aff" rid="af1-biomolecules-05-01122">1</xref><xref ref-type="aff" rid="af2-biomolecules-05-01122">2</xref><xref rid="c1-biomolecules-05-01122" ref-type="corresp">*</xref></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Witt</surname><given-names>Stephan N.</given-names></name><role>Academic Editor</role></contrib></contrib-group><aff id="af1-biomolecules-05-01122"><label>1</label>Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences, No.45 changchun St., Xicheng District, Beijing 100053, China; E-Mail:<email>xushngli_xw@163.com</email></aff><aff id="af2-biomolecules-05-01122"><label>2</label>Parkinson’s disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China</aff><author-notes><corresp id="c1-biomolecules-05-01122"><label>*</label>Author to whom correspondence should be addressed; E-Mail: <email>pbchan90@gmail.com</email>; Tel./Fax: +86-10-8316-1294.</corresp></author-notes><pub-date pub-type="epub"><day>05</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="collection"><month>6</month><year>2015</year></pub-date><volume>5</volume><issue>2</issue><fpage>1122</fpage><lpage>1142</lpage><history><date date-type="received"><day>15</day><month>3</month><year>2015</year></date><date date-type="accepted"><day>29</day><month>4</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 by the authors; licensee MDPI, Basel, Switzerland.</copyright-statement><copyright-year>2015</copyright-year><license><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Parkinson’s disease (PD) is a very common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) into Lewy body (LB) inclusions and the loss of neuronmelanin (NM) containing dopamine (DA) neurons in the substantia nigra (SN). Pathological α-syn and NM are two prominent hallmarks in this selective and progressive neurodegenerative disease. Pathological α-syn can induce dopaminergic neuron death by various mechanisms, such as inducing oxidative stress and inhibiting protein degradation systems. Therefore, to explore the factors that trigger α-syn to convert from a non-toxic protein to toxic one is a pivotal question to clarify the mechanisms of PD pathogenesis. Many triggers for pathological α-syn aggregation have been identified, including missense mutations in the α-syn gene, higher concentration, and posttranslational modifications of α-Syn. Recently, the role of NM in inducing α-syn expression and aggregation has been suggested as a mechanism for this pigment to modulate neuronal vulnerability in PD. NM may be responsible for PD and age-associated increase and aggregation in α-syn. Here, we reviewed our previous study and other recent findings in the area of interaction between NM and α-syn.</p></abstract><kwd-group><kwd>alpha-synuclein</kwd><kwd>Parkinson’s disease</kwd><kwd>neuromelanin</kwd><kwd>oxidative stress</kwd></kwd-group></article-meta></front><body><sec><title>1. Pathological Characteristics and Aetiology of Parkinson’s Disease</title><p>Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The clinical symptoms of PD include motor and non-motor symptoms. The main motor symptoms of PD are bradykinesia (resting tremor), rigidity, and postural instability [<xref rid="B1-biomolecules-05-01122" ref-type="bibr">1</xref>,<xref rid="B2-biomolecules-05-01122" ref-type="bibr">2</xref>,<xref rid="B3-biomolecules-05-01122" ref-type="bibr">3</xref>]. It is believed that the progressive loss of neuromelanin (NM)-containing dopaminergic neurons in the substantia nigra pars compacta (SNpc) is the cause of motor symptoms in PD. Signaling between the SN and the striatum is involved in controlling muscle movements; therefore the resultant loss of nigro-striatal pathway signaling can explain the classical motor symptoms of PD [<xref rid="B2-biomolecules-05-01122" ref-type="bibr">2</xref>,<xref rid="B3-biomolecules-05-01122" ref-type="bibr">3</xref>]. “Dopamine (DA) replacement” pharmacotherapy is relatively effective at reducing the motor disturbances [<xref rid="B4-biomolecules-05-01122" ref-type="bibr">4</xref>]. The non-motor symptoms include autonomic dysfunction (orthostatic hypotension, sphincter disturbances, and/or constipation), cognitive changes, psychiatric effects (depression, psychosis, and/or impulse control disorder), sensory symptoms (pain and/or aching), restlessness, and sleep disturbances [<xref rid="B5-biomolecules-05-01122" ref-type="bibr">5</xref>,<xref rid="B6-biomolecules-05-01122" ref-type="bibr">6</xref>]. These non-motor symptoms may result from disturbances of other neurotransmitter pathways, such as cholinergic, serotonergic, or GABA-ergic and they respond relatively poorly to dopaminergic therapies [<xref rid="B7-biomolecules-05-01122" ref-type="bibr">7</xref>].</p><p>The aetiology of PD is often explained by the interaction between environmental and genetic factors. Environmental studies have identified significant risk factors for PD, such as the exposure to pesticides, herbicide, and metal irons [<xref rid="B8-biomolecules-05-01122" ref-type="bibr">8</xref>]. Many of the recent studies reported that some rare genetic causes of PD relate to the mutations in genes. These genes include SNCA [<xref rid="B9-biomolecules-05-01122" ref-type="bibr">9</xref>,<xref rid="B10-biomolecules-05-01122" ref-type="bibr">10</xref>], the leucine-rich repeat kinase 2 (<italic>LRRK2</italic>) [<xref rid="B11-biomolecules-05-01122" ref-type="bibr">11</xref>], glucocerebrosidase (<italic>GBA</italic>) [<xref rid="B12-biomolecules-05-01122" ref-type="bibr">12</xref>], <italic>Parkin</italic> [<xref rid="B13-biomolecules-05-01122" ref-type="bibr">13</xref>], <italic>DJ-1</italic> [<xref rid="B14-biomolecules-05-01122" ref-type="bibr">14</xref>], <italic>PINK1</italic> [<xref rid="B15-biomolecules-05-01122" ref-type="bibr">15</xref>] <italic>HLA</italic> [<xref rid="B16-biomolecules-05-01122" ref-type="bibr">16</xref>] and <italic>MAPT</italic> [<xref rid="B17-biomolecules-05-01122" ref-type="bibr">17</xref>] genes. In these genetics risk factors for PD, the most important is SNCA; the gene responsible for the expression of α-syn. To date, six PD-linked point mutations in <italic>SNCA</italic> have been identified, comprising the A30P [<xref rid="B18-biomolecules-05-01122" ref-type="bibr">18</xref>], A53T [<xref rid="B19-biomolecules-05-01122" ref-type="bibr">19</xref>], E46K [<xref rid="B20-biomolecules-05-01122" ref-type="bibr">20</xref>], H50Q [<xref rid="B21-biomolecules-05-01122" ref-type="bibr">21</xref>], G51D [<xref rid="B22-biomolecules-05-01122" ref-type="bibr">22</xref>], and A53E [<xref rid="B23-biomolecules-05-01122" ref-type="bibr">23</xref>].</p><p>On the other hand, aging is the biggest known risk factor for the development of idiopathic PD and it is crucial to understand its role. With advancing age, a number of processes essential for the function of SN neurons including DA metabolism, wild type mitochondrial DNA copy number and protein degradation decline [<xref rid="B24-biomolecules-05-01122" ref-type="bibr">24</xref>]. A decline in wild type mtDNA copy number will lead to a decrease in ATP production and a reduction in efficient protein degradation will affect the function of neurons [<xref rid="B25-biomolecules-05-01122" ref-type="bibr">25</xref>]. DA metabolism generates a significant amount of reactive oxygen species that will affect a number of different processes within the neurons [<xref rid="B26-biomolecules-05-01122" ref-type="bibr">26</xref>]. In young and healthy SN neurons, toxic DA metabolic products could be formed in the dark pigment of NM. NM accumulates in double membrane autophagic vacuoles, preventing neurotoxic effects of free neuromelanin in cells exposed to this pigment [<xref rid="B27-biomolecules-05-01122" ref-type="bibr">27</xref>]. However, in aging SN neurons, there is an age-related high content or overall accumulation of NM in the SN. The accumulation NM, which overload of toxic metals or compounds, can potentially result in increased oxidative stress and decreased transformation of toxic DA metabolic products into NM [<xref rid="B28-biomolecules-05-01122" ref-type="bibr">28</xref>]. Moreover, the accumulation of NM may induce the expression and aggregation of α-syn, increasing toxic insults to NM containing SN neurons [<xref rid="B29-biomolecules-05-01122" ref-type="bibr">29</xref>]. NM that leaks from degenerating neurons may contribute to the degeneration of DA neurons in PD by activating microglia [<xref rid="B30-biomolecules-05-01122" ref-type="bibr">30</xref>]. Those toxic mechanisms cause the loss of vulnerable neurons, once this cell loss reaches a certain level, the symptoms of PD develop.</p></sec><sec><title>2. Parkinson’s Disease and α-Synuclein</title><sec><title>2.1. α-Synuclein is Linked to the Pathogenesis of Parkinson’s Disease</title><p>The involvement of α-syn in PD was initially identified through genetic linkage studies in a small number of families [<xref rid="B9-biomolecules-05-01122" ref-type="bibr">9</xref>], including mutations as well as gene duplications [<xref rid="B31-biomolecules-05-01122" ref-type="bibr">31</xref>] and triplications [<xref rid="B32-biomolecules-05-01122" ref-type="bibr">32</xref>]. Up to now, six missense mutations in α-syn gene have been linked to the pathogenesis of PD, comprising A30P, A53T, E46K, H50Q, G51D, and A53E. The A53T and A30P mutations affect the response to oxidative stress, with expression of these mutant isoforms significantly increasing cytotoxicity induced by hydrogen peroxide and 1-methyl-4-phenylpyridinium (MPP+) in comparison to cells expressing wild-type α-syn and control cells [<xref rid="B33-biomolecules-05-01122" ref-type="bibr">33</xref>]. Moreover, the A30P, A53T and H50Q mutations result in increased oligomerization and fibril formation compared to wild-type [<xref rid="B34-biomolecules-05-01122" ref-type="bibr">34</xref>,<xref rid="B35-biomolecules-05-01122" ref-type="bibr">35</xref>], conversely, G51D and A53E mutations reduce the aggregation of α-syn [<xref rid="B36-biomolecules-05-01122" ref-type="bibr">36</xref>,<xref rid="B37-biomolecules-05-01122" ref-type="bibr">37</xref>]. E46K mutation disrupts macroautophagy via inactivation of JNK1-Bcl-2 pathway [<xref rid="B38-biomolecules-05-01122" ref-type="bibr">38</xref>]. Recently, strong association was shown between α-syn and sporadic PD in GWAS [<xref rid="B39-biomolecules-05-01122" ref-type="bibr">39</xref>,<xref rid="B40-biomolecules-05-01122" ref-type="bibr">40</xref>]. α-Syn is also a major component of LBs [<xref rid="B41-biomolecules-05-01122" ref-type="bibr">41</xref>]. These arguments illustrate that α-syn is a central player in the pathogenesis of PD.</p><p>Although the mechanisms by which the genetic variants affect protein pathology remain to be resolved, the processes by which α-syn protein can become pathological are better understood. Under certain conditions, α-syn monomers interact to form prefibrillar or protofibrils, which in turn can form insoluble fibrils [<xref rid="B42-biomolecules-05-01122" ref-type="bibr">42</xref>,<xref rid="B43-biomolecules-05-01122" ref-type="bibr">43</xref>,<xref rid="B44-biomolecules-05-01122" ref-type="bibr">44</xref>]. A widely accepted hypothesis for α-syn toxicity proposes that protofibrils of α-syn are cytotoxic, whereas the fibrillar aggregates of the protein could represent a cytoprotective mechanism in PD [<xref rid="B45-biomolecules-05-01122" ref-type="bibr">45</xref>]. Supporting this hypothesis, α-syn protofibrils are increased in the brains of patients with PD and dementia with Lewy bodies (DLB) [<xref rid="B46-biomolecules-05-01122" ref-type="bibr">46</xref>], and have been associated with neurotoxicity in α-syn overexpressing cells and mouse models [<xref rid="B47-biomolecules-05-01122" ref-type="bibr">47</xref>,<xref rid="B48-biomolecules-05-01122" ref-type="bibr">48</xref>].</p></sec><sec><title>2.2. α-Synuclein and Cytotoxicity</title><p>α-Syn is a 14 kDa natively unfolded protein encoded by the <italic>SNCA</italic> gene that is highly conserved in vertebrate species, and the small protein is abundantly expressed in the brain as well as in multiple other central and peripheral tissues [<xref rid="B49-biomolecules-05-01122" ref-type="bibr">49</xref>]. Maroteaux <italic>et al.</italic> [<xref rid="B50-biomolecules-05-01122" ref-type="bibr">50</xref>] first described the localization of α-syn to the nucleus and the presynaptic terminal. Although the exact function of α-syn remains unknown, substantial evidence suggest that α-syn associates with vesicular and membranous structures and plays a role in synaptic vesicle recycling, and storage and compartmentalization of neurotransmitters [<xref rid="B51-biomolecules-05-01122" ref-type="bibr">51</xref>]. The α-syn peptide has 140 amino acids, with three distinct regions: a N-terminal (1–60 residues) that contain four imperfect repeats of KTKEGV motifs; a NAC region (61–95 residues), with three additional KTKEGV repeats; and the hydrophobic and amyloidogenic NAC region, a C-terminus (96–140 residues) that is enriched in acidic and proline residues, and that facilitates interactions with different proteins [<xref rid="B52-biomolecules-05-01122" ref-type="bibr">52</xref>] (see <xref ref-type="fig" rid="biomolecules-05-01122-f001">Figure 1</xref>). All three regions are necessary for the misfolding of the protein.</p><p>The conformation of α-syn is highly dependent on environmental conditions. Indeed, despite the overwhelming evidence that α-syn is a disordered monomer in solution, two recent reports suggest that the native protein exists as a helical tetramer with a molecular weight of about 58 kDa under physiological conditions, with reduced aggregation tendencies, and that the dissociation of the tetramer into monomeric subunits promotes toxic aggregation [<xref rid="B53-biomolecules-05-01122" ref-type="bibr">53</xref>,<xref rid="B54-biomolecules-05-01122" ref-type="bibr">54</xref>]. What is more certain is the α-syn protein adopts oligomeric and/or fibrillar conformations in certain pathological conditions [<xref rid="B55-biomolecules-05-01122" ref-type="bibr">55</xref>,<xref rid="B56-biomolecules-05-01122" ref-type="bibr">56</xref>,<xref rid="B57-biomolecules-05-01122" ref-type="bibr">57</xref>] (such as mutations in the SNCA gene, structural modification produced by environmental changes, mistakes on the post-translational modifications and induction of protein misfolding by seeding or cross-seeding mechanisms).</p><fig id="biomolecules-05-01122-f001" position="float"><label>Figure 1</label><caption><p>α-Synuclein (α-syn) protein domain structure. α-Syn is a 140 amino acid protein and its sequence can be divided into three regions with distinct structural characteristics. The highly conserved N-terminal domain encodes for a series of imperfect 11 amino acid repeats with a consensus motif of KTKEGV reminiscent of the lipid-binding domain of apolipoproteins, which in certain conditions forms amphipathic helices. The six missense mutations known to cause familial PD (A30P, E46K, H50Q, G51D, A53E and A53T) lie in the amphipathic region, suggesting an important function for this region of the protein. The central hydrophobic region (non-amyloid-β component or NAC domain) of α-synuclein is associated with an increased propensity of the protein to form fibrils [<xref rid="B58-biomolecules-05-01122" ref-type="bibr">58</xref>]. The acidic C-terminal tail contains mostly negatively charged residues and is largely unfolded.</p></caption><graphic xlink:href="biomolecules-05-01122-g001"></graphic></fig><p>Up to now, although the precise mechanisms of cytotoxicity of α-syn are still not fully understood, abundant evidence suggests that the toxic effect of α-syn involves many different mechanisms: (i) loss of the normal function of α-syn in neurotransmission release, especially in the regulating DA release [<xref rid="B59-biomolecules-05-01122" ref-type="bibr">59</xref>,<xref rid="B60-biomolecules-05-01122" ref-type="bibr">60</xref>,<xref rid="B61-biomolecules-05-01122" ref-type="bibr">61</xref>,<xref rid="B62-biomolecules-05-01122" ref-type="bibr">62</xref>,<xref rid="B63-biomolecules-05-01122" ref-type="bibr">63</xref>], leads to the selective dysfunction or degeneration of DA neurons in PD; (ii) α-Syn impairs mitochondrial structure and inhibits complex I activity, promoting the production of reactive oxygen species (ROS) [<xref rid="B64-biomolecules-05-01122" ref-type="bibr">64</xref>,<xref rid="B65-biomolecules-05-01122" ref-type="bibr">65</xref>,<xref rid="B66-biomolecules-05-01122" ref-type="bibr">66</xref>,<xref rid="B67-biomolecules-05-01122" ref-type="bibr">67</xref>,<xref rid="B68-biomolecules-05-01122" ref-type="bibr">68</xref>]; (iii) α-Syn disrupts ER-Golgi vesicular transport and results in toxic ER stress [<xref rid="B69-biomolecules-05-01122" ref-type="bibr">69</xref>,<xref rid="B70-biomolecules-05-01122" ref-type="bibr">70</xref>,<xref rid="B71-biomolecules-05-01122" ref-type="bibr">71</xref>]; (iv) α-Syn inhibits protein degradation systems, including ubiquitin-proteasomal system (UPS) and Autophagy-lysosome system [<xref rid="B72-biomolecules-05-01122" ref-type="bibr">72</xref>], interferes with the normal physiology of the cell, and eventually leads to cell injury and death; (v) α-Syn promotes the permeabilization of membranes and disrupts cellular homeostasis [<xref rid="B73-biomolecules-05-01122" ref-type="bibr">73</xref>]; (vi) α-Syn induces the increase of ROS by direct or indirect interaction with oxidative stress [<xref rid="B74-biomolecules-05-01122" ref-type="bibr">74</xref>]; and (vii) “prion-like” propagation, by which pathological α-syn aggregates are propagated between connected brain regions via a cell-to-cell transmission mechanism, which is an important mechanism to induce progressive DA neurons loss in PD [<xref rid="B75-biomolecules-05-01122" ref-type="bibr">75</xref>].</p></sec><sec><title>2.3. α-Synuclein Post-Translational Modifications</title><p>Several post-translational modifications of α-syn may occur, such as phosphorylation, truncation, ubiquitination, nitration. Studies investigating the phosphorylation of α-syn in diseased and aged brains have shown that α-syn can be phosphorylated at serines (S87, S129) as well as at several tyrosines, including Y125, Y133, and Y136. The pS129 modification is most often correlated with PD pathology. This notion is primarily supported by the finding that the majority of α-syn in LBs in postmortem PD brains is phosphorylated at S129 (pS129) [<xref rid="B76-biomolecules-05-01122" ref-type="bibr">76</xref>,<xref rid="B77-biomolecules-05-01122" ref-type="bibr">77</xref>]. The S129 phosphorylation of α-syn in aggregates has also been observed in animal models of PD [<xref rid="B78-biomolecules-05-01122" ref-type="bibr">78</xref>,<xref rid="B79-biomolecules-05-01122" ref-type="bibr">79</xref>]. Although a few studies reported that overexpression of the phosphorylated serine 129 isoform in animal models does not produce toxicity [<xref rid="B80-biomolecules-05-01122" ref-type="bibr">80</xref>,<xref rid="B81-biomolecules-05-01122" ref-type="bibr">81</xref>], most evidence suggests that phosphorylation of α-syn at serine 129 to promote its aggregation and neurotoxicity [<xref rid="B82-biomolecules-05-01122" ref-type="bibr">82</xref>]. Mechanistic studies have shown that aggregated forms of α-syn are more prone to phosphorylation and that pS129 phosphorylated aggregates accumulate as the disease progresses [<xref rid="B83-biomolecules-05-01122" ref-type="bibr">83</xref>,<xref rid="B84-biomolecules-05-01122" ref-type="bibr">84</xref>,<xref rid="B85-biomolecules-05-01122" ref-type="bibr">85</xref>], suggesting that the degree of α-syn pS129 phosphorylation is an indicator of disease progression. The link between S129 phosphorylation and PD pathology has fueled an interest in modulating α-syn phosphorylation at S129 as a potential therapy for PD. Multiple kinases have been identified which phosphorylate α-syn at S129, with most evidence pointing to polo-like kinase 2 (PLK2) as the primary phosphorylated of α-syn S129 [<xref rid="B86-biomolecules-05-01122" ref-type="bibr">86</xref>]. A straightforward therapeutic approach based on reducing α-syn phospho-S129 would be to inhibit PLK 2 kinase activity; however some contradictory findings should be taken into account. For instance, overexpression of PLK 2 in rat brain using adeno-associated viral vectors can suppress α-syn toxicity by promoting autophagy-mediated degradation of phospho-S129 α-syn [<xref rid="B87-biomolecules-05-01122" ref-type="bibr">87</xref>]. Therefore, therapies based on modulating α-syn phospho-S129 appear to require an optimal phosphorylation level rather than a complete dephosphorylation.</p><p>The majority of ubiquinated α-syn is mono- to tri-ubiquinated, and while poly-ubiquitination serves as a signal for α-syn degradation by the proteasome, it does not seem to be required for α-syn fibrillation and LB formation [<xref rid="B88-biomolecules-05-01122" ref-type="bibr">88</xref>]. Nevertheless, an interplay between phosphorylation and ubiquitination may render the protein more susceptible to aggregation [<xref rid="B89-biomolecules-05-01122" ref-type="bibr">89</xref>]. Small amounts of various C-terminal truncated forms of α-syn have been detected in LBs, which exhibit greater fibrillation capacity [<xref rid="B90-biomolecules-05-01122" ref-type="bibr">90</xref>]. Oxidation leads to other common post-translational modifications, including nitrosylation, and it has been shown that oxidative stress can stabilize oligomeric α-syn species via the formation of di-tyrosine cross-links [<xref rid="B91-biomolecules-05-01122" ref-type="bibr">91</xref>].</p></sec><sec><title>2.4. α-Synuclein and Oxidative Stress</title><p>Abundant evidence suggests that there is a potential interaction between α-syn and oxidative stress. Some studies have found that oxidative stress induces up-regulation of the expression of α-syn, and promotes its fibrillization and aggregation [<xref rid="B92-biomolecules-05-01122" ref-type="bibr">92</xref>]. Conversely, a high degree of fibrillization and aggregation of α-syn results in an increase of reactive oxygen species (ROS) and neurotoxicity [<xref rid="B93-biomolecules-05-01122" ref-type="bibr">93</xref>]. It is believed that a vicious cycle between α-syn and oxidative stress may play a pivotal role in the progressive loss of SN dopaminergic neurons in PD. For example, incubation of recombinant α-syn with cytochrome c in the presence of H<sub>2</sub>O<sub>2</sub> [<xref rid="B94-biomolecules-05-01122" ref-type="bibr">94</xref>], or exposure of cells in culture to H<sub>2</sub>O<sub>2</sub> and ferrous iron, MPP+, NO and superoxide promotes α-syn aggregation [<xref rid="B58-biomolecules-05-01122" ref-type="bibr">58</xref>,<xref rid="B95-biomolecules-05-01122" ref-type="bibr">95</xref>,<xref rid="B96-biomolecules-05-01122" ref-type="bibr">96</xref>]. Additionally, oxidative stress can cause nuclear membrane modifications and α-syn translocation to the nucleus where it can form complexes with histones leading to its oligomerization into insoluble fibrils [<xref rid="B97-biomolecules-05-01122" ref-type="bibr">97</xref>,<xref rid="B98-biomolecules-05-01122" ref-type="bibr">98</xref>,<xref rid="B99-biomolecules-05-01122" ref-type="bibr">99</xref>]. On the other hand, aggregation and high levels of α-syn have been shown to induce oxidant production or increase the level of oxidative stress. As a result, experiments with cultured cells or animal models have demonstrated that over-expression of wild-type or mutant α-syn increases sensitivity to DA, MPTP and 6-OHDA toxicity [<xref rid="B100-biomolecules-05-01122" ref-type="bibr">100</xref>,<xref rid="B101-biomolecules-05-01122" ref-type="bibr">101</xref>,<xref rid="B102-biomolecules-05-01122" ref-type="bibr">102</xref>,<xref rid="B103-biomolecules-05-01122" ref-type="bibr">103</xref>]. Conversely, mice lacking α-syn demonstrate marked resistance to MPTP and other mitochondrial toxins such as malonate and 3-nitropropionic acid [<xref rid="B104-biomolecules-05-01122" ref-type="bibr">104</xref>,<xref rid="B105-biomolecules-05-01122" ref-type="bibr">105</xref>]. Addition of exogenous α-syn fibrils in culture medium or injecting it into the brain can led to selective decreases in synaptic proteins, progressive impairments in neuronal excitability and connectivity, and eventually, neuron death. These results suggest that oxidative stress promotes α-syn aggregation, which in turn increases oxidative stress level, creating a vicious cycle leading to neurodegeneration.</p></sec></sec><sec><title>3. Parkinson’s Disease and Neuromelanin</title><sec><title>3.1. Neuromelanin Structure and Biosynthesis</title><p>NM is the dark insoluble macromolecule that confers the black (SN) or grey (locus coeruleus) color to monoaminergic basal ganglia. It is a polymer pigment synthesized that contains catecholamine-based compounds such as oxidized DA, DA metabolites as well as proteins and lipids. Histological studies showed that NM granules were located in the neuronal perikaryon and were surrounded by a double membrane [<xref rid="B106-biomolecules-05-01122" ref-type="bibr">106</xref>]. In the SN, NM accumulates during aging and is found after the first two to three years of life [<xref rid="B107-biomolecules-05-01122" ref-type="bibr">107</xref>]. X-ray diffraction studies have shown that NM has a multilayer (graphite-like) three-dimensional structure similar to synthetic and naturally occurring melanin [<xref rid="B108-biomolecules-05-01122" ref-type="bibr">108</xref>]. The three-dimensional structure is derived from planar overlapped sheets consisting of cyclic molecules of indole benzothiazine rings. However, these sheets are stacked much higher in NM than in any other synthetic and naturally occurring melanin [<xref rid="B108-biomolecules-05-01122" ref-type="bibr">108</xref>].</p><p>Biosynthesis of NM may due to tyrosine hydroxylase-mediated oxidation of DA [<xref rid="B109-biomolecules-05-01122" ref-type="bibr">109</xref>] or auto-oxidation of DA [<xref rid="B110-biomolecules-05-01122" ref-type="bibr">110</xref>]. Although the process of NM formation is obscure, a recent <italic>in vitro</italic> study has clearly established some steps of this complex process [<xref rid="B111-biomolecules-05-01122" ref-type="bibr">111</xref>]. The study demonstrated that NM synthesis was induced in rat SN neurons and PC12 cell cultures by exposure to L-dopa. The pigment produced in this model contains a stable free radical; in addition, both light and electron microscopy have shown that the pigment synthesized in these cells appears to be identical to human NM, and the granules are surrounded by a double membrane, similar to the naturally occurring NM of the SN. In this model, NM synthesis was shown to be driven by an excess of cytosolic catecholamines.</p></sec><sec><title>3.2. Neuromelanin Involved in the Pathogenesis of Parkinson’s Disease</title><p>Although the role of NM remains unclear, especially in the SN, both under physiological conditions and in the pathogenesis of PD, it is a fact that NM containing neurons in SN are more vulnerable than the non-pigmented ones in PD. Normally, NM is considered to play a protective role intracellular by binding toxic metabolite produced in SN cells such as oxidized DA, DA metabolites and metals [<xref rid="B112-biomolecules-05-01122" ref-type="bibr">112</xref>,<xref rid="B113-biomolecules-05-01122" ref-type="bibr">113</xref>,<xref rid="B114-biomolecules-05-01122" ref-type="bibr">114</xref>] and serve as an antioxidant [<xref rid="B115-biomolecules-05-01122" ref-type="bibr">115</xref>,<xref rid="B116-biomolecules-05-01122" ref-type="bibr">116</xref>]. However, it has been also suggested that NM can be potentially toxic to DA neurons, by directly inhibiting proteasomes function [<xref rid="B117-biomolecules-05-01122" ref-type="bibr">117</xref>], and catalyzing the production of free radicals [<xref rid="B118-biomolecules-05-01122" ref-type="bibr">118</xref>]. NM might also become a source of free radicals by reaction with hydrogen peroxide [<xref rid="B119-biomolecules-05-01122" ref-type="bibr">119</xref>,<xref rid="B120-biomolecules-05-01122" ref-type="bibr">120</xref>]. Changed structure and density of NM have been found in early PD, suggesting that NM may play role in the pathogenesis in PD. Analysis of NM in the SN of PD patients has shown an early accumulation and overload of iron, which can potentially result in increased oxidative stress [<xref rid="B121-biomolecules-05-01122" ref-type="bibr">121</xref>]. The interaction of NM with α-syn has also been suggested as a mechanism for this pigment to modulate neuronal vulnerability [<xref rid="B74-biomolecules-05-01122" ref-type="bibr">74</xref>]. α-Syn is over-expressed in individual melanized neurons [<xref rid="B29-biomolecules-05-01122" ref-type="bibr">29</xref>], and its aggregates redistribute to NM in the SN early in PD but not in healthy controls [<xref rid="B121-biomolecules-05-01122" ref-type="bibr">121</xref>]. Moreover, NM that leaks from degenerating neurons may contribute to the neurodegenerative process by activating microglia [<xref rid="B122-biomolecules-05-01122" ref-type="bibr">122</xref>]. The activated microglia produces proinflammatory cytokines such as TNF-α, IL-6 and NO and may involve in PD pathogenesis [<xref rid="B123-biomolecules-05-01122" ref-type="bibr">123</xref>].</p></sec><sec><title>3.3. Interaction of Neuromelanin with Organic or Inorganic Molecules</title><p>NM interacts with numerous organic and inorganic molecules including lipids, pesticides, toxic compounds and metal ions [<xref rid="B124-biomolecules-05-01122" ref-type="bibr">124</xref>]. NM might reduce the toxicity of MPTP by accumulating its toxic metabolite MPP+ <italic>in vivo</italic> [<xref rid="B125-biomolecules-05-01122" ref-type="bibr">125</xref>]. The herbicide paraquat has a molecular structure similar to that of MPTP, and has been proposed as a Parkinson’s disease inducing agent. The pesticide is accumulated in NM containing nerve cells, where it appears that the NM adsorbed intraneuronal paraquat, protecting the neurons from consequent damage [<xref rid="B126-biomolecules-05-01122" ref-type="bibr">126</xref>]. NM can also accumulate chlorpromazine, haloperidol, and imipramine, thereby contributing to the control of the intraneuronal concentration of these molecules. Because higher intraneuronal concentrations of dopaminergic drugs might be toxic to substantia nigra neurons, NM can influence this toxicity [<xref rid="B127-biomolecules-05-01122" ref-type="bibr">127</xref>]. The association of NM with lipids has been described in several studies [<xref rid="B128-biomolecules-05-01122" ref-type="bibr">128</xref>,<xref rid="B129-biomolecules-05-01122" ref-type="bibr">129</xref>,<xref rid="B130-biomolecules-05-01122" ref-type="bibr">130</xref>]. Although previous studies proposed that lipids were part of the NM molecule, recent work has shown that NM contains about 20% adsorbed lipids. Cholesterol is a minor component in this lipid mixture, with the major component being a new class of polyunsaturated lipid with a high molecular mass, low volatility, and low oxygen content [<xref rid="B129-biomolecules-05-01122" ref-type="bibr">129</xref>]. It may be that NM itself catalyzes the synthesis of this type of lipid. Alternatively, NM could originate from lipofuscin by an enzymatic reaction occurring in lysosomes [<xref rid="B131-biomolecules-05-01122" ref-type="bibr">131</xref>], although this hypothesis is not supported by previous observations [<xref rid="B123-biomolecules-05-01122" ref-type="bibr">123</xref>]. In this case, high molecular mass lipids could be derived from a lysosomal metabolic pathway and might interact with NM within these organelles. The ability of NM to bind different types of organic compounds may influence the intracellular role of lipids and proteins.</p><p>High concentrations of iron and other non-alkaline metals are present in several brain nuclei. NM from the SN can interact with many heavy metal ions such as zinc, copper, manganese, chromium, cobalt, mercury, lead, and cadmium; in addition, it binds iron particularly strongly [<xref rid="B132-biomolecules-05-01122" ref-type="bibr">132</xref>,<xref rid="B133-biomolecules-05-01122" ref-type="bibr">133</xref>]. In the course of PD, the concentration of iron in the SN increases by 30%–35%. This accumulation of SN iron seems to occur within the NM granules: the concentration of iron in these granules is higher in patients with PD than in normal subjects [<xref rid="B134-biomolecules-05-01122" ref-type="bibr">134</xref>]. It seems that the amount of iron bound to NM determines whether this molecule acts as a protective agent blocking redox active metal ions or whether in the presence of excess iron it promotes the formation of cytotoxic radicals [<xref rid="B135-biomolecules-05-01122" ref-type="bibr">135</xref>,<xref rid="B136-biomolecules-05-01122" ref-type="bibr">136</xref>]. The ability of NM to chelate other redox active metals such as copper, manganese, chromium, and toxic metals including cadmium, mercury, and lead [<xref rid="B133-biomolecules-05-01122" ref-type="bibr">133</xref>] strengthens the hypothesis that NM may be a high capacity storage trapping system for metal ions and, as such, may prevent neuronal damage. The capacity of NM to form stable complexes with toxic exogenous metals and redox active metals seems to play a protective role even if such a capability can in principle be saturated by high cytosolic concentrations of metals.</p></sec></sec><sec><title>4. Interaction between α-Synuclein and Neuromelanin</title><sec><title>4.1. Accumulation of Nenromelanin Increases the Level of α-Synuclein in SN Neurons</title><p>NM is considered to play a protective role as a scavenger to clear toxic metabolite produced in SN neurons. However, it has been also suggested that NM can be potentially toxic to DA neurons, by directly inhibiting proteasomal function and catalyzing the production of free radicals [<xref rid="B127-biomolecules-05-01122" ref-type="bibr">127</xref>]. Recently, several studies suggested NM induces the expression or aggregation of α-syn in DA neurons of SN in aging or PD brain [<xref rid="B29-biomolecules-05-01122" ref-type="bibr">29</xref>,<xref rid="B115-biomolecules-05-01122" ref-type="bibr">115</xref>,<xref rid="B137-biomolecules-05-01122" ref-type="bibr">137</xref>,<xref rid="B138-biomolecules-05-01122" ref-type="bibr">138</xref>]. Fasano <italic>et al.</italic> reported that NM directly binds with α-syn in residual SN neurons of PD [<xref rid="B139-biomolecules-05-01122" ref-type="bibr">139</xref>]. The fact that α-syn is expressed in melanoma and nevus, but not in non-melanocytic cutaneous carcinoma and normal skin, suggests that melanin may induce the expression of α-syn [<xref rid="B138-biomolecules-05-01122" ref-type="bibr">138</xref>]. Moreover, α-syn mRNA levels were detected significantly elevated in individual NM-containing DA neurons from PD midbrain when compared to those from matched controls, further supporting the notion of NM induces the expression of α-syn [<xref rid="B137-biomolecules-05-01122" ref-type="bibr">137</xref>]. NM also increases the accumulation of α-syn in DA neurons. Halliday GM <italic>et al.</italic> reported that more vulnerable SN A9 neurons with normal morphological appearance exhibited significantly increased NM density associated with a concentration of α-syn to the lipid component of NM in early PD patients [<xref rid="B115-biomolecules-05-01122" ref-type="bibr">115</xref>]. The increased concentration of neuronal NM and α-syn in normal A9 neurons may already predispose these neurons to precipitate α-syn around NM-associated lipid under oxidative conditions. These changes may trigger a cascade of events leading to larger intracellular aggregates of α-syn and eventually lead to the death of those NM-containing DA neurons in PD [<xref rid="B115-biomolecules-05-01122" ref-type="bibr">115</xref>]. In addition to PD brain, our previous study found that NM accumulation also induces expression of α-syn during aging in NM-containing DA neurons and leads to age related loss of DA neurons [<xref rid="B29-biomolecules-05-01122" ref-type="bibr">29</xref>]. In our previous study, the marked increase in NM and α-syn in aged individuals suggests that NM content may be essential for α-syn over-expression [<xref rid="B29-biomolecules-05-01122" ref-type="bibr">29</xref>]. We found that accumulation of NM in SN starts very early in life [<xref rid="B140-biomolecules-05-01122" ref-type="bibr">140</xref>], whereas the detectable pathogenic accumulation of α-syn begins around middle age [<xref rid="B141-biomolecules-05-01122" ref-type="bibr">141</xref>] in the same area. Although both regions contain DA neurons and are closely localized to one another, it has been reported that α-syn accumulates with age in the SN but not in the ventral tegmental area (VTA) [<xref rid="B141-biomolecules-05-01122" ref-type="bibr">141</xref>]. An important difference between the VTA and the SN is that the dopaminergic neurons in the SN contain significantly more NM than those in the VTA. This further supports the notion that NM may be responsible for age-associated increases in α-syn.</p><p>Although growing evidence suggests that excessive accumulation of NM may initiate gathering of α-syn, the precise mechanism is still unclear. Findings to date suggested that iron saturated NM produces many free radical species and increases oxidative insults [<xref rid="B142-biomolecules-05-01122" ref-type="bibr">142</xref>], which may initiate gathering of α-syn. Alternatively, accumulated NM could induce proteasome inhibition [<xref rid="B111-biomolecules-05-01122" ref-type="bibr">111</xref>,<xref rid="B143-biomolecules-05-01122" ref-type="bibr">143</xref>] and result in a reduction of α-syn clearance. Further, NM may be synergistic with other factors that promote age-related “autophagic stress” [<xref rid="B144-biomolecules-05-01122" ref-type="bibr">144</xref>] and thereby influence the degradation of α-syn [<xref rid="B145-biomolecules-05-01122" ref-type="bibr">145</xref>].</p></sec><sec><title>4.2. α-Synuclein Induces the Biosynthesis of Neuromelanin</title><p>Pan <italic>et al.</italic> [<xref rid="B146-biomolecules-05-01122" ref-type="bibr">146</xref>] reported that over-expressed α-syn increased the content of NM in SH-SY5Y and PC12 dopaminergic cells, suggesting α-syn may promote the biosynthesis of NM in DA neurons. However, the precise mechanisms of α-syn induce biosynthesis of NM is still unclear. At present, it has been accepted that the formation of NM is due to either enzymatically mediated or auto-oxidation of DA pathway [<xref rid="B147-biomolecules-05-01122" ref-type="bibr">147</xref>]. So far, tyrosinase, tyrosine hydroxylase (TH), peroxidase, prostaglandin H synthase, and macrophage migration inhibitory factor were suggested to be involved in NM synthesis [<xref rid="B148-biomolecules-05-01122" ref-type="bibr">148</xref>]. However, there is currently no general agreement on the role eventually played by any of these enzymes in the synthesis of NM in SN neurons [<xref rid="B147-biomolecules-05-01122" ref-type="bibr">147</xref>]. Although the role of these enzymes in the synthesis of NM is not known for sure, current studies indicate that α-syn modulates the activities of some of them, such as tyrosinase [<xref rid="B149-biomolecules-05-01122" ref-type="bibr">149</xref>], tyrosine hydroxylase (TH) [<xref rid="B150-biomolecules-05-01122" ref-type="bibr">150</xref>], and peroxidase [<xref rid="B151-biomolecules-05-01122" ref-type="bibr">151</xref>]. α-Syn may affect the biosynthesis of NM by regulating these enzyme activities.</p><p>On the other hand, NM could derive from non-enzymatic oxidation. The auto-oxidation of catechols to quinones with the subsequent addition of thiol groups has been demonstrated in the brain [<xref rid="B152-biomolecules-05-01122" ref-type="bibr">152</xref>]. An <italic>in vitro</italic> study clarified some steps of the complex biosynthesis of NM in cultured dopaminergic neuronal cells [<xref rid="B123-biomolecules-05-01122" ref-type="bibr">123</xref>]. NM synthesis could be induced in rat SN and in PC12 cells in culture by exposure to L-DOPA, which is rapidly converted in DA in the cytosol. The pigment produced in this model was chemically identical to human NM as demonstrated by EPR. Moreover, it was localized in characteristic organelles surrounded by a double membrane, as is similar to naturally occurring NM [<xref rid="B123-biomolecules-05-01122" ref-type="bibr">123</xref>]. Moreover, NM synthesis could be inhibited by the adenoviral-mediated over-expression of the synaptic vesicular monoamine transporter 2 (VMAT2), which sequesters monoamines from the cytosol into synaptic vesicles for subsequent neurotransmission [<xref rid="B153-biomolecules-05-01122" ref-type="bibr">153</xref>], suggesting that an excess of cytosolic free catecholamines is an essential factor for the synthesis of NM. The high concentration of NM in SN neurons seems to be linked to the presence of considerable amounts of cytosolic dopamine that have not been sequestered into synaptic vesicles [<xref rid="B123-biomolecules-05-01122" ref-type="bibr">123</xref>].</p><p>Abundant evidence has proved that α-syn is involved in regulating DA homeostasis and affecting the levels of cytosolic DA. α-Syn may modulate DA homeostasis through multiple mechanisms, such as synthesis, storage, release and reuptake [<xref rid="B101-biomolecules-05-01122" ref-type="bibr">101</xref>]. α-Syn regulates the biosynthesis of DA by inhibiting the activity of tyrosine hydroxylase (TH) [<xref rid="B154-biomolecules-05-01122" ref-type="bibr">154</xref>], the rate-limiting enzyme responsible for converting tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in the DA synthesis pathway. Overexpression of α-syn has also been reported to decrease the rate of DA release, both in mouse and cell culture models [<xref rid="B155-biomolecules-05-01122" ref-type="bibr">155</xref>,<xref rid="B156-biomolecules-05-01122" ref-type="bibr">156</xref>]. α-Syn can direct bind to DAT via its C-terminal domain and enhance extracellular DA uptake by increasing the number of functional transporters at the cell surface [<xref rid="B157-biomolecules-05-01122" ref-type="bibr">157</xref>,<xref rid="B158-biomolecules-05-01122" ref-type="bibr">158</xref>]. Enhanced extracellular DA uptake increases the levels of cytosolic DA. More importantly, α-syn may affect the storage of DA by regulating vesicle docking and recycling at the nerve terminal, increasing permeability of secretory vesicles and decreasing the levels of VMAT2. This could prevent incorporation of newly synthesized and newly taken up DA into vesicles and lead to increase the level of cytosolic DA [<xref rid="B159-biomolecules-05-01122" ref-type="bibr">159</xref>]. The notion is supported by some studies that found α-syn mutation or overexpression lead to elevated cytosolic DA [<xref rid="B160-biomolecules-05-01122" ref-type="bibr">160</xref>,<xref rid="B161-biomolecules-05-01122" ref-type="bibr">161</xref>]. The cytosolic DA can be metabolized in mitochondria by monoamine oxidase (MAO). If these processes are insufficient to control cytosolic DA homeostasis, excess cytoslic DA can be oxidized to quinones and semiquinones via iron catalysis in the cytosol. These quinones react with Cys residues in proteins, such as α-syn [<xref rid="B162-biomolecules-05-01122" ref-type="bibr">162</xref>], to form DA-Cys-protein adducts, which are phagocytized in autophagic vacuoles (AG). Because of a low level of lysosomal fusion and/or to a buildup of undegradable DA-adducts, even in the presence of lysosomal hydrolases, over time the vacuoles become NM granules [<xref rid="B148-biomolecules-05-01122" ref-type="bibr">148</xref>]. So, α-syn may induce the biosynthesis of NM by increasing the levels of cytosolic DA.</p></sec></sec><sec><title>5. Conclusions</title><p>The pathological characteristics of PD are progressive loss of neuromelanin (NM)-containing dopaminergic neurons in SNpc and α-syn positive LBs in survival neurons. Abundant evidence has proved that α-syn play a pivotal role in the pathogenesis of PD. Missense mutations in α-syn gene could result in early onset familial PD. The toxicity of abnormal α-syn forms to DA neurons and loss of normal functions of this protein are important causes in the pathogenesis in sporadic PD. NM is a dark, complex, and insoluble pigment granule in several types of neurons of the central nervous system that is particularly concentrated in the DA neurons of SN and in the noradrenergic neurons of locus coeruleus [<xref rid="B127-biomolecules-05-01122" ref-type="bibr">127</xref>]. Although the mechanism is not clear, SN and the locus coeruleus are the two brain areas mostly affected by PD. This fact draws a close attention to NM and its possible involvement in neurodegenerative processes. Recently, several studies suggested that the interaction of NM with α-syn may be a mechanism for this pigment to modulate neuronal vulnerability. α-Syn is over-expressed in individual melanized neurons [<xref rid="B29-biomolecules-05-01122" ref-type="bibr">29</xref>,<xref rid="B137-biomolecules-05-01122" ref-type="bibr">137</xref>,<xref rid="B138-biomolecules-05-01122" ref-type="bibr">138</xref>] and its aggregates redistribute to NM in the SN early in PD but not in healthy controls [<xref rid="B115-biomolecules-05-01122" ref-type="bibr">115</xref>]. On the other hand, α-syn also induces the biosynthesis of NM by increasing the levels of cytosolic DA [<xref rid="B146-biomolecules-05-01122" ref-type="bibr">146</xref>].</p><p>In conclusion, no matter what is the trigger, NM and α-syn are likely to form a vicious cycle of mutual promotion, eventually the untoward cycle results in the death of DA neurons in PD (see <xref ref-type="fig" rid="biomolecules-05-01122-f002">Figure 2</xref>). In sporadic PD, age-related accumulation of NM induces α-syn expression and aggregation. On the other hand, accumulated α-syn may promote the biosynthesis of NM by increasing the levels of cytosolic DA. In familial PD, the mutants of α-syn also can trigger the accumulation of NM and start this vicious cycle.</p><fig id="biomolecules-05-01122-f002" position="float"><label>Figure 2</label><caption><p>Model of possible interactions between α-synuclein (α-syn) and neuromelanin (NM). (<bold>a</bold>) NM induces the expression and aggregation of α-syn; (<bold>b</bold>) dopamine (DA) is synthesized in the cytoplasm by the action of tyrosine hydroxylase (TH) and amino acid decarboxylase (AADC). α-Syn has been shown to regulate the activity of TH and AADC; (<bold>c</bold>) DA is reuptake via the dopamine transporter (DAT). Studies in cell culture systems have shown that α-syn is necessary for the trafficking of DAT to the cell surface. (<bold>d</bold>) Once synthesized, DA is immediately sequestered into vesicles by the vesicular monoamine transporter 2 (VMAT2). Several lines of evidence suggest that α-syn is involved in regulating storage, release and presynaptic vesicle cycling. (<bold>e</bold>) High levels of α-syn and cytosolic DA cause selective DA neuron death and eventually lead to PD.</p></caption><graphic xlink:href="biomolecules-05-01122-g002"></graphic></fig></sec></body><back><ack><title>Acknowledgments</title><p>We are grateful to the National Natural Science Foundation for financial support (No. 81171298).</p></ack><notes><title>Author Contributions</title><p>Both Shengli Xu and Piu Chan contributed to reviewing the literature, and to the writing of this manuscript.</p></notes><notes><title>Conflicts of Interest</title><p>The authors declare no conflict of interest.</p></notes><ref-list><title>References</title><ref id="B1-biomolecules-05-01122"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Olanow</surname><given-names>C.W.</given-names></name><name><surname>Tatton</surname><given-names>W.G.</given-names></name></person-group><article-title>Etiology and pathogenesis of Parkinson’s disease</article-title><source>Annu. Rev. Neurosci.</source><year>1999</year><volume>22</volume><fpage>123</fpage><lpage>144</lpage><pub-id pub-id-type="doi">10.1146/annurev.neuro.22.1.123</pub-id><pub-id pub-id-type="pmid">10202534</pub-id></element-citation></ref><ref id="B2-biomolecules-05-01122"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sulzer</surname><given-names>D.</given-names></name><name><surname>Surmeier</surname><given-names>D.J.</given-names></name></person-group><article-title>Neuronal vulnerability, pathogenesis, and Parkinson’s disease</article-title><source>Mov. Disord.</source><year>2013</year><volume>28</volume><fpage>41</fpage><lpage>50</lpage><pub-id pub-id-type="doi">10.1002/mds.25095</pub-id><pub-id pub-id-type="pmid">22791686</pub-id></element-citation></ref><ref id="B3-biomolecules-05-01122"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fahn</surname><given-names>S.</given-names></name><name><surname>Sulzer</surname><given-names>D.</given-names></name></person-group><article-title>Neurodegeneration and neuroprotection in Parkinson disease</article-title><source>NeuroRx</source><year>2004</year><volume>1</volume><fpage>139</fpage><lpage>154</lpage><pub-id pub-id-type="doi">10.1602/neurorx.1.1.139</pub-id><pub-id pub-id-type="pmid">15717014</pub-id></element-citation></ref><ref id="B4-biomolecules-05-01122"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Poewe</surname><given-names>W.</given-names></name><name><surname>Antonini</surname><given-names>A.</given-names></name><name><surname>Zijlmans</surname><given-names>J.C.</given-names></name><name><surname>Burkhard</surname><given-names>P.R.</given-names></name><name><surname>Vingerhoets</surname><given-names>F.</given-names></name></person-group><article-title>Levodopa in the treatment of Parkinson’s disease: An old drug still going strong</article-title><source>Clin. Interv. Aging</source><year>2010</year><volume>7</volume><fpage>229</fpage><lpage>238</lpage><pub-id pub-id-type="pmid">20852670</pub-id></element-citation></ref><ref id="B5-biomolecules-05-01122"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gonera</surname><given-names>E.G.</given-names></name><name><surname>Van’t Hof</surname><given-names>M.</given-names></name><name><surname>Berger</surname><given-names>H.J.</given-names></name><name><surname>van Weel</surname><given-names>C.</given-names></name><name><surname>Horstink</surname><given-names>M.W.</given-names></name></person-group><article-title>Symptoms and duration of the prodromal phase in Parkinson’s disease</article-title><source>Mov. Disord.</source><year>1997</year><volume>12</volume><fpage>871</fpage><lpage>876</lpage><pub-id pub-id-type="doi">10.1002/mds.870120607</pub-id><pub-id pub-id-type="pmid">9399209</pub-id></element-citation></ref><ref id="B6-biomolecules-05-01122"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ziemssen</surname><given-names>T.</given-names></name><name><surname>Reichmann</surname><given-names>H.</given-names></name></person-group><article-title>Non-motor dysfunction in Parkinson’s disease</article-title><source>Park. Relat. Disord.</source><year>2007</year><volume>13</volume><fpage>323</fpage><lpage>332</lpage><pub-id pub-id-type="doi">10.1016/j.parkreldis.2006.12.014</pub-id><pub-id pub-id-type="pmid">17349813</pub-id></element-citation></ref><ref id="B7-biomolecules-05-01122"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maass</surname><given-names>A.</given-names></name><name><surname>Reichmann</surname><given-names>H.</given-names></name></person-group><article-title>Sleep and non-motor symptoms in Parkinson’s disease</article-title><source>J. Neural Transm.</source><year>2013</year><volume>120</volume><fpage>565</fpage><lpage>569</lpage><pub-id pub-id-type="doi">10.1007/s00702-013-0966-4</pub-id><pub-id pub-id-type="pmid">23338671</pub-id></element-citation></ref><ref id="B8-biomolecules-05-01122"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jenner</surname><given-names>P.</given-names></name><name><surname>Morris</surname><given-names>H.R.</given-names></name><name><surname>Robbins</surname><given-names>T.W.</given-names></name><name><surname>Goedert</surname><given-names>M.</given-names></name><name><surname>Hardy</surname><given-names>J.</given-names></name><name><surname>Ben-Shlomo</surname><given-names>Y.</given-names></name><name><surname>Bolam</surname><given-names>P.</given-names></name><name><surname>Burn</surname><given-names>D.</given-names></name><name><surname>Hindle</surname><given-names>J.V.</given-names></name><name><surname>Brooks</surname><given-names>D.</given-names></name></person-group><article-title>Parkinson’s disease—The debate on the clinical phenomenology, aetiology, pathology and pathogenesis</article-title><source>J. Parkinsons Dis.</source><year>2013</year><volume>3</volume><fpage>1</fpage><lpage>11</lpage><pub-id pub-id-type="pmid">23938306</pub-id></element-citation></ref><ref id="B9-biomolecules-05-01122"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Polymeropoulos</surname><given-names>M.H.</given-names></name><name><surname>Lavedan</surname><given-names>C.</given-names></name><name><surname>Leroy</surname><given-names>E.</given-names></name><name><surname>Ide</surname><given-names>S.E.</given-names></name><name><surname>Dehejia</surname><given-names>A.</given-names></name><name><surname>Dutra</surname><given-names>A.</given-names></name><name><surname>Pike</surname><given-names>B.</given-names></name><name><surname>Root</surname><given-names>H.</given-names></name><name><surname>Rubenstein</surname><given-names>J.</given-names></name><name><surname>Boyer</surname><given-names>R.</given-names></name><etal></etal></person-group><article-title>Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease</article-title><source>Science</source><year>1997</year><volume>276</volume><fpage>2045</fpage><lpage>2047</lpage><pub-id pub-id-type="doi">10.1126/science.276.5321.2045</pub-id><pub-id pub-id-type="pmid">9197268</pub-id></element-citation></ref><ref id="B10-biomolecules-05-01122"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Singleton</surname><given-names>A.B.</given-names></name><name><surname>Farrer</surname><given-names>M.</given-names></name><name><surname>Johnson</surname><given-names>J.</given-names></name><name><surname>Singleton</surname><given-names>A.</given-names></name><name><surname>Hague</surname><given-names>S.</given-names></name><name><surname>Kachergus</surname><given-names>J.</given-names></name><name><surname>Hulihan</surname><given-names>M.</given-names></name><name><surname>Peuralinna</surname><given-names>T.</given-names></name><name><surname>Dutra</surname><given-names>A.</given-names></name><name><surname>Nussbaum</surname><given-names>R.</given-names></name><etal></etal></person-group><article-title>α-Synuclein locus triplication causes Parkinson’s disease</article-title><source>Science</source><year>2003</year><pub-id pub-id-type="doi">10.1126/science.1090278</pub-id></element-citation></ref><ref id="B11-biomolecules-05-01122"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zimprich</surname><given-names>A.</given-names></name><name><surname>Biskup</surname><given-names>S.</given-names></name><name><surname>Leitner</surname><given-names>P.</given-names></name><name><surname>Lichtner</surname><given-names>P.</given-names></name><name><surname>Farrer</surname><given-names>M.</given-names></name><name><surname>Lincoln</surname><given-names>S.</given-names></name><name><surname>Kachergus</surname><given-names>J.</given-names></name><name><surname>Hulihan</surname><given-names>M.</given-names></name><name><surname>Uitti</surname><given-names>R.J.</given-names></name><name><surname>Calne</surname><given-names>D.B.</given-names></name><etal></etal></person-group><article-title>Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology</article-title><source>Neuron</source><year>2004</year><volume>44</volume><fpage>601</fpage><lpage>607</lpage><pub-id pub-id-type="doi">10.1016/j.neuron.2004.11.005</pub-id><pub-id pub-id-type="pmid">15541309</pub-id></element-citation></ref><ref id="B12-biomolecules-05-01122"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Westbroek</surname><given-names>W.</given-names></name><name><surname>Gustafson</surname><given-names>A.M.</given-names></name><name><surname>Sidransky</surname><given-names>E.</given-names></name></person-group><article-title>Exploring the link between glucocerebrosidase mutations and parkinsonism</article-title><source>Trends Mol. Med.</source><year>2011</year><volume>17</volume><fpage>485</fpage><lpage>493</lpage><pub-id pub-id-type="doi">10.1016/j.molmed.2011.05.003</pub-id><pub-id pub-id-type="pmid">21723784</pub-id></element-citation></ref><ref id="B13-biomolecules-05-01122"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gouider-Khouja</surname><given-names>N.</given-names></name><name><surname>Larnaout</surname><given-names>A.</given-names></name><name><surname>Amouri</surname><given-names>R.</given-names></name><name><surname>Sfar</surname><given-names>S.</given-names></name><name><surname>Belal</surname><given-names>S.</given-names></name><name><surname>Ben Hamida</surname><given-names>C.</given-names></name><name><surname>Ben Hamida</surname><given-names>M.</given-names></name><name><surname>Hattori</surname><given-names>N.</given-names></name><name><surname>Mizuno</surname><given-names>Y.</given-names></name><name><surname>Hentati</surname><given-names>F.</given-names></name></person-group><article-title>Autosomal recessive parkinsonism linked to parkin gene in a Tunisian family. Clinical, genetic and pathological study</article-title><source>Park. Relat. Disord.</source><year>2003</year><volume>9</volume><fpage>247</fpage><lpage>251</lpage><pub-id pub-id-type="doi">10.1016/S1353-8020(03)00016-6</pub-id></element-citation></ref><ref id="B14-biomolecules-05-01122"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bonifati</surname><given-names>V.</given-names></name><name><surname>Rizzu</surname><given-names>P.</given-names></name><name><surname>van Baren</surname><given-names>M.J.</given-names></name><name><surname>Schaap</surname><given-names>O.</given-names></name><name><surname>Breedveld</surname><given-names>G.J.</given-names></name><name><surname>Krieger</surname><given-names>E.</given-names></name><name><surname>Dekker</surname><given-names>M.C.</given-names></name><name><surname>Squitieri</surname><given-names>F.</given-names></name><name><surname>Ibanez</surname><given-names>P.</given-names></name><name><surname>Joosse</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism</article-title><source>Science</source><year>2003</year><volume>299</volume><fpage>256</fpage><lpage>259</lpage><pub-id pub-id-type="doi">10.1126/science.1077209</pub-id><pub-id pub-id-type="pmid">12446870</pub-id></element-citation></ref><ref id="B15-biomolecules-05-01122"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Valente</surname><given-names>E.M.</given-names></name><name><surname>Abou-Sleiman</surname><given-names>P.M.</given-names></name><name><surname>Caputo</surname><given-names>V.</given-names></name><name><surname>Muqit</surname><given-names>M.M.</given-names></name><name><surname>Harvey</surname><given-names>K.</given-names></name><name><surname>Gispert</surname><given-names>S.</given-names></name><name><surname>Ali</surname><given-names>Z.</given-names></name><name><surname>del Turco</surname><given-names>D.</given-names></name><name><surname>Bentivoglio</surname><given-names>A.R.</given-names></name><name><surname>Healy</surname><given-names>D.G.</given-names></name><etal></etal></person-group><article-title>Hereditary early-onset Parkinson’s disease caused by mutations in PINK1</article-title><source>Science</source><year>2004</year><volume>304</volume><fpage>1158</fpage><lpage>1160</lpage><pub-id pub-id-type="doi">10.1126/science.1096284</pub-id><pub-id pub-id-type="pmid">15087508</pub-id></element-citation></ref><ref id="B16-biomolecules-05-01122"><label>16.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hamza</surname><given-names>T.H.</given-names></name><name><surname>Zabetian</surname><given-names>C.P.</given-names></name><name><surname>Tenesa</surname><given-names>A.</given-names></name><name><surname>Laederach</surname><given-names>A.</given-names></name><name><surname>Montimurro</surname><given-names>J.</given-names></name><name><surname>Yearout</surname><given-names>D.</given-names></name><name><surname>Kay</surname><given-names>D.M.</given-names></name><name><surname>Doheny</surname><given-names>K.F.</given-names></name><name><surname>Paschall</surname><given-names>J.</given-names></name><name><surname>Pugh</surname><given-names>E.</given-names></name><etal></etal></person-group><article-title>Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease</article-title><source>Nat. Genet.</source><year>2010</year><volume>42</volume><fpage>781</fpage><lpage>785</lpage><pub-id pub-id-type="doi">10.1038/ng.642</pub-id><pub-id pub-id-type="pmid">20711177</pub-id></element-citation></ref><ref id="B17-biomolecules-05-01122"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Skipper</surname><given-names>L.</given-names></name><name><surname>Wilkes</surname><given-names>K.</given-names></name><name><surname>Toft</surname><given-names>M.</given-names></name><name><surname>Baker</surname><given-names>M.</given-names></name><name><surname>Lincoln</surname><given-names>S.</given-names></name><name><surname>Hulihan</surname><given-names>M.</given-names></name><name><surname>Ross</surname><given-names>O.A.</given-names></name><name><surname>Hutton</surname><given-names>M.</given-names></name><name><surname>Aasly</surname><given-names>J.</given-names></name><name><surname>Farrer</surname><given-names>M.</given-names></name></person-group><article-title>Linkage disequilibrium and association of MAPT H1 in Parkinson disease</article-title><source>Am. J. Hum. Genet.</source><year>2004</year><volume>75</volume><fpage>669</fpage><lpage>677</lpage><pub-id pub-id-type="doi">10.1086/424492</pub-id><pub-id pub-id-type="pmid">15297935</pub-id></element-citation></ref><ref id="B18-biomolecules-05-01122"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jensen</surname><given-names>P.H.</given-names></name><name><surname>Nielsen</surname><given-names>M.S.</given-names></name><name><surname>Jakes</surname><given-names>R.</given-names></name><name><surname>Dotti</surname><given-names>C.G.</given-names></name><name><surname>Goedert</surname><given-names>M.</given-names></name></person-group><article-title>Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson’s disease mutation</article-title><source>J. Biol. Chem.</source><year>1998</year><volume>273</volume><fpage>26292</fpage><lpage>26294</lpage><pub-id pub-id-type="doi">10.1074/jbc.273.41.26292</pub-id><pub-id pub-id-type="pmid">9756856</pub-id></element-citation></ref><ref id="B19-biomolecules-05-01122"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Farrer</surname><given-names>M.</given-names></name><name><surname>Wavrant-De Vrieze</surname><given-names>F.</given-names></name><name><surname>Crook</surname><given-names>R.</given-names></name><name><surname>Boles</surname><given-names>L.</given-names></name><name><surname>Perez-Tur</surname><given-names>J.</given-names></name><name><surname>Hardy</surname><given-names>J.</given-names></name><name><surname>Johnson</surname><given-names>W.G.</given-names></name><name><surname>Steele</surname><given-names>J.</given-names></name><name><surname>Maraganore</surname><given-names>D.</given-names></name><name><surname>Gwinn</surname><given-names>K.</given-names></name><etal></etal></person-group><article-title>Low frequency of alpha-synuclein mutations in familial Parkinson’s disease</article-title><source>Ann. Neurol.</source><year>1998</year><volume>43</volume><fpage>394</fpage><lpage>397</lpage><pub-id pub-id-type="doi">10.1002/ana.410430320</pub-id><pub-id pub-id-type="pmid">9506559</pub-id></element-citation></ref><ref id="B20-biomolecules-05-01122"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zarranz</surname><given-names>J.J.</given-names></name><name><surname>Alegre</surname><given-names>J.</given-names></name><name><surname>Gómez-Esteban</surname><given-names>J.C.</given-names></name><name><surname>Lezcano</surname><given-names>E.</given-names></name><name><surname>Ros</surname><given-names>R.</given-names></name><name><surname>Ampuero</surname><given-names>I.</given-names></name><name><surname>Vidal</surname><given-names>L.</given-names></name><name><surname>Hoenicka</surname><given-names>J.</given-names></name><name><surname>Rodriguez</surname><given-names>O.</given-names></name><name><surname>Atarés</surname><given-names>B.</given-names></name><etal></etal></person-group><article-title>The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia</article-title><source>Ann. Neurol.</source><year>2004</year><volume>55</volume><fpage>164</fpage><lpage>173</lpage><pub-id pub-id-type="doi">10.1002/ana.10795</pub-id><pub-id pub-id-type="pmid">14755719</pub-id></element-citation></ref><ref id="B21-biomolecules-05-01122"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Proukakis</surname><given-names>C.</given-names></name><name><surname>Dudzik</surname><given-names>C.G.</given-names></name><name><surname>Brier</surname><given-names>T.</given-names></name><name><surname>MacKay</surname><given-names>D.S.</given-names></name><name><surname>Cooper</surname><given-names>J.M.</given-names></name><name><surname>Millhauser</surname><given-names>G.L.</given-names></name><name><surname>Houlden</surname><given-names>H.</given-names></name><name><surname>Schapira</surname><given-names>A.H.</given-names></name></person-group><article-title>A novel α-synuclein missense mutation in Parkinson disease</article-title><source>Neurology</source><year>2013</year><volume>80</volume><fpage>1062</fpage><lpage>1064</lpage><pub-id pub-id-type="doi">10.1212/WNL.0b013e31828727ba</pub-id><pub-id pub-id-type="pmid">23427326</pub-id></element-citation></ref><ref id="B22-biomolecules-05-01122"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kiely</surname><given-names>A.P.</given-names></name><name><surname>Asi</surname><given-names>Y.T.</given-names></name><name><surname>Kara</surname><given-names>E.</given-names></name><name><surname>Limousin</surname><given-names>P.</given-names></name><name><surname>Ling</surname><given-names>H.</given-names></name><name><surname>Lewis</surname><given-names>P.</given-names></name><name><surname>Proukakis</surname><given-names>C.</given-names></name><name><surname>Quinn</surname><given-names>N.</given-names></name><name><surname>Lees</surname><given-names>A.J.</given-names></name><name><surname>Hardy</surname><given-names>J.</given-names></name><etal></etal></person-group><article-title>α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson’s disease and multiple system atrophy?</article-title><source>Acta Neuropathol.</source><year>2013</year><volume>125</volume><fpage>753</fpage><lpage>769</lpage><pub-id pub-id-type="doi">10.1007/s00401-013-1096-7</pub-id><pub-id pub-id-type="pmid">23404372</pub-id></element-citation></ref><ref id="B23-biomolecules-05-01122"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pasanen</surname><given-names>P.</given-names></name><name><surname>Myllykangas</surname><given-names>L.</given-names></name><name><surname>Siitonen</surname><given-names>M.</given-names></name><name><surname>Raunio</surname><given-names>A.</given-names></name><name><surname>Kaakkola</surname><given-names>S.</given-names></name><name><surname>Lyytinen</surname><given-names>J.</given-names></name><name><surname>Tienari</surname><given-names>P.J.</given-names></name><name><surname>Pöyhönen</surname><given-names>M.</given-names></name><name><surname>Paetau</surname><given-names>A.</given-names></name></person-group><article-title>Novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson’s disease-type pathology</article-title><source>Neurobiol. Aging</source><year>2014</year><volume>35</volume><fpage>2180.e1</fpage><lpage>2180.e5</lpage><pub-id pub-id-type="doi">10.1016/j.neurobiolaging.2014.03.024</pub-id><pub-id pub-id-type="pmid">24746362</pub-id></element-citation></ref><ref id="B24-biomolecules-05-01122"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reeve</surname><given-names>A.</given-names></name><name><surname>Simcox</surname><given-names>E.</given-names></name><name><surname>Turnbull</surname><given-names>D.</given-names></name></person-group><article-title>Ageing and Parkinson’s disease: Why is advancing age the biggest risk factor?</article-title><source>Ageing Res. Rev.</source><year>2014</year><volume>14</volume><fpage>19</fpage><lpage>30</lpage><pub-id pub-id-type="doi">10.1016/j.arr.2014.01.004</pub-id><pub-id pub-id-type="pmid">24503004</pub-id></element-citation></ref><ref id="B25-biomolecules-05-01122"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Subramaniam</surname><given-names>S.R.</given-names></name><name><surname>Chesselet</surname><given-names>M.F.</given-names></name></person-group><article-title>Mitochondrial dysfunction and oxidative stress in Parkinson’s disease</article-title><source>Prog. Neurobiol.</source><year>2013</year><volume>106–107</volume><fpage>17</fpage><lpage>32</lpage><pub-id pub-id-type="doi">10.1016/j.pneurobio.2013.04.004</pub-id><pub-id pub-id-type="pmid">23643800</pub-id></element-citation></ref><ref id="B26-biomolecules-05-01122"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mosharov</surname><given-names>E.V.</given-names></name><name><surname>Larsen</surname><given-names>K.E.</given-names></name><name><surname>Kanter</surname><given-names>E.</given-names></name><name><surname>Phillips</surname><given-names>K.A.</given-names></name><name><surname>Wilson</surname><given-names>K.</given-names></name><name><surname>Schmitz</surname><given-names>Y.</given-names></name><name><surname>Krantz</surname><given-names>D.E.</given-names></name><name><surname>Kobayashi</surname><given-names>K.</given-names></name><name><surname>Edwards</surname><given-names>R.H.</given-names></name><name><surname>Sulzer</surname><given-names>D.</given-names></name></person-group><article-title>Interplay between cytosolic dopamine, calcium, and alpha-synuclein cause selective death of substantia nigra neurons</article-title><source>Neuron</source><year>2009</year><volume>62</volume><fpage>218</fpage><lpage>229</lpage><pub-id pub-id-type="doi">10.1016/j.neuron.2009.01.033</pub-id><pub-id pub-id-type="pmid">19409267</pub-id></element-citation></ref><ref id="B27-biomolecules-05-01122"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Muñoz</surname><given-names>P.</given-names></name><name><surname>Huenchuguala</surname><given-names>S.</given-names></name><name><surname>Paris</surname><given-names>I.</given-names></name><name><surname>Segura-Aguilar</surname><given-names>J.</given-names></name></person-group><article-title>Dopamine oxidation and autophagy</article-title><source>Park. Dis.</source><year>2012</year><pub-id pub-id-type="doi">10.1155/2012/920953</pub-id><pub-id pub-id-type="pmid">22966478</pub-id></element-citation></ref><ref id="B28-biomolecules-05-01122"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sulzer</surname><given-names>D.</given-names></name><name><surname>Mosharov</surname><given-names>E.</given-names></name><name><surname>Talloczy</surname><given-names>Z.</given-names></name><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Simon</surname><given-names>J.D.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name></person-group><article-title>Neuronal pigmented autophagic vacuoles: Lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease</article-title><source>J. Neurochem.</source><year>2008</year><volume>106</volume><fpage>24</fpage><lpage>36</lpage><pub-id pub-id-type="doi">10.1111/j.1471-4159.2008.05385.x</pub-id><pub-id pub-id-type="pmid">18384642</pub-id></element-citation></ref><ref id="B29-biomolecules-05-01122"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xuan</surname><given-names>Q.</given-names></name><name><surname>Xu</surname><given-names>S.L.</given-names></name><name><surname>Lu</surname><given-names>D.H.</given-names></name><name><surname>Yu</surname><given-names>S.</given-names></name><name><surname>Zhou</surname><given-names>M.</given-names></name><name><surname>Uéda</surname><given-names>K.</given-names></name><name><surname>Cui</surname><given-names>Y.Q.</given-names></name><name><surname>Zhang</surname><given-names>B.Y.</given-names></name><name><surname>Chan</surname><given-names>P.</given-names></name></person-group><article-title>Increased expression of α-synuclein in aged human brain associated with neuromelanin accumulation</article-title><source>J. Neural Transm.</source><year>2011</year><volume>118</volume><fpage>1575</fpage><lpage>1583</lpage><pub-id pub-id-type="doi">10.1007/s00702-011-0636-3</pub-id><pub-id pub-id-type="pmid">21461961</pub-id></element-citation></ref><ref id="B30-biomolecules-05-01122"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>W.</given-names></name><name><surname>Phillips</surname><given-names>K.</given-names></name><name><surname>Wielgus</surname><given-names>A.R.</given-names></name><name><surname>Liu</surname><given-names>J.</given-names></name><name><surname>Albertini</surname><given-names>A.</given-names></name><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Faust</surname><given-names>R.</given-names></name><name><surname>Qian</surname><given-names>S.Y.</given-names></name><name><surname>Miller</surname><given-names>D.S.</given-names></name><name><surname>Chignell</surname><given-names>C.F.</given-names></name><etal></etal></person-group><article-title>Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: Implications for progression of Parkinson’s disease</article-title><source>Neurotox. Res.</source><year>2011</year><volume>19</volume><fpage>63</fpage><lpage>72</lpage><pub-id pub-id-type="doi">10.1007/s12640-009-9140-z</pub-id><pub-id pub-id-type="pmid">19957214</pub-id></element-citation></ref><ref id="B31-biomolecules-05-01122"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chartier-Harlin</surname><given-names>M.C.</given-names></name><name><surname>Kachergus</surname><given-names>J.</given-names></name><name><surname>Roumier</surname><given-names>C.</given-names></name><name><surname>Mouroux</surname><given-names>V.</given-names></name><name><surname>Douay</surname><given-names>X.</given-names></name><name><surname>Lincoln</surname><given-names>S.</given-names></name><name><surname>Levecque</surname><given-names>C.</given-names></name><name><surname>Larvor</surname><given-names>L.</given-names></name><name><surname>Andrieux</surname><given-names>J.</given-names></name><name><surname>Hulihan</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease</article-title><source>Lancet</source><year>2004</year><volume>364</volume><fpage>1167</fpage><lpage>1169</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(04)17103-1</pub-id><pub-id pub-id-type="pmid">15451224</pub-id></element-citation></ref><ref id="B32-biomolecules-05-01122"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Byers</surname><given-names>B.</given-names></name><name><surname>Cord</surname><given-names>B.</given-names></name><name><surname>Nguyen</surname><given-names>H.N.</given-names></name><name><surname>Schüle</surname><given-names>B.</given-names></name><name><surname>Fenno</surname><given-names>L.</given-names></name><name><surname>Lee</surname><given-names>P.C.</given-names></name><name><surname>Deisseroth</surname><given-names>K.</given-names></name><name><surname>Langston</surname><given-names>J.W.</given-names></name><name><surname>Pera</surname><given-names>R.R.</given-names></name><name><surname>Palmer</surname><given-names>T.D.</given-names></name></person-group><article-title>SNCA triplication Parkinson’s patient’s iPSC-derived DA neurons accumulate α-synuclein and are susceptible to oxidative stress</article-title><source>PLoS ONE</source><year>2011</year><volume>6</volume><fpage>e26159</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0026159</pub-id><pub-id pub-id-type="pmid">22110584</pub-id></element-citation></ref><ref id="B33-biomolecules-05-01122"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kanda</surname><given-names>S.</given-names></name><name><surname>Bishop</surname><given-names>J.F.</given-names></name><name><surname>Eglitis</surname><given-names>M.A.</given-names></name><name><surname>Yang</surname><given-names>Y.</given-names></name><name><surname>Mouradian</surname><given-names>M.M.</given-names></name></person-group><article-title>Enhanced viability to oxidative stress by alpha-synuclein mutations and C-terminal truncation</article-title><source>Neuroscience</source><year>2000</year><volume>97</volume><fpage>279</fpage><lpage>284</lpage><pub-id pub-id-type="doi">10.1016/S0306-4522(00)00077-4</pub-id><pub-id pub-id-type="pmid">10799759</pub-id></element-citation></ref><ref id="B34-biomolecules-05-01122"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Narhi</surname><given-names>L.</given-names></name><name><surname>Wood</surname><given-names>S.J.</given-names></name><name><surname>Steavenson</surname><given-names>S.</given-names></name><name><surname>Jiang</surname><given-names>Y.</given-names></name><name><surname>Wu</surname><given-names>G.M.</given-names></name><name><surname>Anafi</surname><given-names>D.</given-names></name><name><surname>Kaufman</surname><given-names>S.A.</given-names></name><name><surname>Martin</surname><given-names>F.</given-names></name><name><surname>Sitney</surname><given-names>K.</given-names></name><name><surname>Denis</surname><given-names>P.</given-names></name><etal></etal></person-group><article-title>Both familial Parkinson’s disease mutations accelerate alpha-synuclein aggregation</article-title><source>J. Biol. Chem.</source><year>1999</year><volume>274</volume><fpage>9843</fpage><lpage>9846</lpage><pub-id pub-id-type="doi">10.1074/jbc.274.14.9843</pub-id><pub-id pub-id-type="pmid">10092675</pub-id></element-citation></ref><ref id="B35-biomolecules-05-01122"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khalaf</surname><given-names>O.</given-names></name><name><surname>Fauvet</surname><given-names>B.</given-names></name><name><surname>Oueslati</surname><given-names>A.</given-names></name><name><surname>Dikiy</surname><given-names>I.</given-names></name><name><surname>Mahul-Mellier</surname><given-names>A.L.</given-names></name><name><surname>Ruggeri</surname><given-names>F.S.</given-names></name><name><surname>Mbefo</surname><given-names>M.</given-names></name><name><surname>Vercruysse</surname><given-names>F.</given-names></name><name><surname>Dietler</surname><given-names>G.</given-names></name><name><surname>Lee</surname><given-names>S.J.</given-names></name><etal></etal></person-group><article-title>The H50Q mutation enhances α-synuclein aggregation, secretion and toxicity</article-title><source>J. Biol. Chem.</source><year>2014</year><volume>289</volume><fpage>21856</fpage><lpage>21876</lpage><pub-id pub-id-type="pmid">24936070</pub-id></element-citation></ref><ref id="B36-biomolecules-05-01122"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rutherford</surname><given-names>N.J.</given-names></name><name><surname>Moore</surname><given-names>B.D.</given-names></name><name><surname>Golde</surname><given-names>T.E.</given-names></name><name><surname>Giasson</surname><given-names>B.I.</given-names></name></person-group><article-title>Divergent effects of the H50Q and G51D SNCA mutations on the aggregation of α-synuclein</article-title><source>J. Neurochem.</source><year>2014</year><volume>131</volume><fpage>859</fpage><lpage>867</lpage><pub-id pub-id-type="doi">10.1111/jnc.12806</pub-id><pub-id pub-id-type="pmid">24984882</pub-id></element-citation></ref><ref id="B37-biomolecules-05-01122"><label>37.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ghosh</surname><given-names>D.</given-names></name><name><surname>Sahay</surname><given-names>S.</given-names></name><name><surname>Ranjan</surname><given-names>P.</given-names></name><name><surname>Salot</surname><given-names>S.</given-names></name><name><surname>Mohite</surname><given-names>G.M.</given-names></name><name><surname>Singh</surname><given-names>P.K.</given-names></name><name><surname>Dwivedi</surname><given-names>S.</given-names></name><name><surname>Carvalho</surname><given-names>E.</given-names></name><name><surname>Banerjee</surname><given-names>R.</given-names></name><name><surname>Kumar</surname><given-names>A.</given-names></name><etal></etal></person-group><article-title>The newly discovered Parkinson’s disease associated Finnish mutation (A53E) attenuates α-synuclein aggregation and membrane binding</article-title><source>Biochemistry</source><year>2014</year><volume>53</volume><fpage>6419</fpage><lpage>6421</lpage><pub-id pub-id-type="doi">10.1021/bi5010365</pub-id><pub-id pub-id-type="pmid">25268550</pub-id></element-citation></ref><ref id="B38-biomolecules-05-01122"><label>38.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yan</surname><given-names>J.Q.</given-names></name><name><surname>Yuan</surname><given-names>Y.H.</given-names></name><name><surname>Gao</surname><given-names>Y.N.</given-names></name><name><surname>Huang</surname><given-names>J.Y.</given-names></name><name><surname>Ma</surname><given-names>K.L.</given-names></name><name><surname>Gao</surname><given-names>Y.</given-names></name><name><surname>Zhang</surname><given-names>W.Q.</given-names></name><name><surname>Guo</surname><given-names>X.F.</given-names></name><name><surname>Chen</surname><given-names>N.H.</given-names></name></person-group><article-title>Overexpression of human E46K mutant α-synuclein impairs macroautophagy via inactivation of JNK1-Bcl-2 pathway</article-title><source>Mol. Neurobiol.</source><year>2014</year><volume>50</volume><fpage>685</fpage><lpage>701</lpage><pub-id pub-id-type="doi">10.1007/s12035-014-8738-1</pub-id><pub-id pub-id-type="pmid">24833599</pub-id></element-citation></ref><ref id="B39-biomolecules-05-01122"><label>39.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ramanan</surname><given-names>V.K.</given-names></name><name><surname>Saykin</surname><given-names>A.J.</given-names></name></person-group><article-title>Pathways to neurodegeneration: Mechanistic insights from GWAS in Alzheimer’s disease, Parkinson’s disease, and related disorders</article-title><source>Am. J. Neurodegener. Dis.</source><year>2013</year><volume>18</volume><fpage>145</fpage><lpage>175</lpage><pub-id pub-id-type="pmid">24093081</pub-id></element-citation></ref><ref id="B40-biomolecules-05-01122"><label>40.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Satake</surname><given-names>W.</given-names></name><name><surname>Nakabayashi</surname><given-names>Y.</given-names></name><name><surname>Mizuta</surname><given-names>I.</given-names></name><name><surname>Hirota</surname><given-names>Y.</given-names></name><name><surname>Ito</surname><given-names>C.</given-names></name><name><surname>Kubo</surname><given-names>M.</given-names></name><name><surname>Kawaguchi</surname><given-names>T.</given-names></name><name><surname>Tsunoda</surname><given-names>T.</given-names></name><name><surname>Watanabe</surname><given-names>M.</given-names></name><name><surname>Takeda</surname><given-names>A.</given-names></name><etal></etal></person-group><article-title>Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease</article-title><source>Nat. Genet.</source><year>2009</year><volume>41</volume><fpage>1303</fpage><lpage>1307</lpage><pub-id pub-id-type="doi">10.1038/ng.485</pub-id><pub-id pub-id-type="pmid">19915576</pub-id></element-citation></ref><ref id="B41-biomolecules-05-01122"><label>41.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Spillantini</surname><given-names>M.G.</given-names></name><name><surname>Schmidt</surname><given-names>M.L.</given-names></name><name><surname>Lee</surname><given-names>V.M.</given-names></name><name><surname>Trojanowski</surname><given-names>J.Q.</given-names></name><name><surname>Jakes</surname><given-names>R.</given-names></name><name><surname>Goedert</surname><given-names>M.</given-names></name></person-group><article-title>α-Synuclein in Lewy bodies</article-title><source>Nature</source><year>1997</year><volume>388</volume><fpage>839</fpage><lpage>840</lpage><pub-id pub-id-type="doi">10.1038/42166</pub-id><pub-id pub-id-type="pmid">9278044</pub-id></element-citation></ref><ref id="B42-biomolecules-05-01122"><label>42.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>N.Y.</given-names></name><name><surname>Tang</surname><given-names>Z.</given-names></name><name><surname>Liu</surname><given-names>C.W.</given-names></name></person-group><article-title>α-Synuclein protofibrils inhibit 26 S proteasome-mediated protein degradation: Understanding the cytotoxicity of protein protofibrils in neurodegenerative disease pathogenesis</article-title><source>J. Biol. Chem.</source><year>2008</year><volume>283</volume><fpage>20288</fpage><lpage>20298</lpage><pub-id pub-id-type="doi">10.1074/jbc.M710560200</pub-id><pub-id pub-id-type="pmid">18502751</pub-id></element-citation></ref><ref id="B43-biomolecules-05-01122"><label>43.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lashuel</surname><given-names>H.A.</given-names></name><name><surname>Grillo-Bosch</surname><given-names>D.</given-names></name></person-group><article-title><italic>In vitro</italic> preparation of prefibrillar intermediates of amyloid-beta and alpha-synuclein</article-title><source>Methods Mol. Biol.</source><year>2005</year><volume>299</volume><fpage>19</fpage><lpage>33</lpage><pub-id pub-id-type="pmid">15980593</pub-id></element-citation></ref><ref id="B44-biomolecules-05-01122"><label>44.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cole</surname><given-names>N.B.</given-names></name><name><surname>Murphy</surname><given-names>D.D.</given-names></name><name><surname>Lebowitz</surname><given-names>J.</given-names></name><name><surname>Di Noto</surname><given-names>L.</given-names></name><name><surname>Levine</surname><given-names>R.L.</given-names></name><name><surname>Nussbaum</surname><given-names>R.L.</given-names></name></person-group><article-title>Metal-catalyzed oxidation of alpha-synuclein: Helping to define the relationship between oligomers, protofibrils, and filaments</article-title><source>J. Biol. Chem.</source><year>2005</year><volume>280</volume><fpage>9678</fpage><lpage>9690</lpage><pub-id pub-id-type="doi">10.1074/jbc.M409946200</pub-id><pub-id pub-id-type="pmid">15615715</pub-id></element-citation></ref><ref id="B45-biomolecules-05-01122"><label>45.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wakabayashi</surname><given-names>K.</given-names></name><name><surname>Tanji</surname><given-names>K.</given-names></name><name><surname>Mori</surname><given-names>F.</given-names></name><name><surname>Takahashi</surname><given-names>H.</given-names></name></person-group><article-title>The Lewy body in Parkinson’s disease: Molecules implicated in the formation and degradation of alpha-synuclein aggregates</article-title><source>Neuropathology</source><year>2007</year><volume>27</volume><fpage>494</fpage><lpage>506</lpage><pub-id pub-id-type="doi">10.1111/j.1440-1789.2007.00803.x</pub-id><pub-id pub-id-type="pmid">18018486</pub-id></element-citation></ref><ref id="B46-biomolecules-05-01122"><label>46.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fagerqvist</surname><given-names>T.</given-names></name><name><surname>Lindström</surname><given-names>V.</given-names></name><name><surname>Nordström</surname><given-names>E.</given-names></name><name><surname>Lord</surname><given-names>A.</given-names></name><name><surname>Tucker</surname><given-names>S.M.</given-names></name><name><surname>Su</surname><given-names>X.</given-names></name><name><surname>Sahlin</surname><given-names>C.</given-names></name><name><surname>Kasrayan</surname><given-names>A.</given-names></name><name><surname>Andersson</surname><given-names>J.</given-names></name><name><surname>Welander</surname><given-names>H.</given-names></name><etal></etal></person-group><article-title>Monoclonal antibodies selective for α-synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation</article-title><source>J. Neurochem.</source><year>2013</year><volume>126</volume><fpage>131</fpage><lpage>144</lpage><pub-id pub-id-type="doi">10.1111/jnc.12175</pub-id><pub-id pub-id-type="pmid">23363402</pub-id></element-citation></ref><ref id="B47-biomolecules-05-01122"><label>47.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>H.J.</given-names></name><name><surname>Lee</surname><given-names>S.J.</given-names></name></person-group><article-title>Characterization of cytoplasmic alpha-synuclein aggregates. Fibril formation is tightly linked to the inclusion-forming process in cells</article-title><source>J. Biol. Chem.</source><year>2002</year><volume>277</volume><fpage>48976</fpage><lpage>48983</lpage><pub-id pub-id-type="doi">10.1074/jbc.M208192200</pub-id><pub-id pub-id-type="pmid">12351642</pub-id></element-citation></ref><ref id="B48-biomolecules-05-01122"><label>48.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lindström</surname><given-names>V.</given-names></name><name><surname>Fagerqvist</surname><given-names>T.</given-names></name><name><surname>Nordström</surname><given-names>E.</given-names></name><name><surname>Eriksson</surname><given-names>F.</given-names></name><name><surname>Lord</surname><given-names>A.</given-names></name><name><surname>Tucker</surname><given-names>S.</given-names></name><name><surname>Andersson</surname><given-names>J.</given-names></name><name><surname>Johannesson</surname><given-names>M.</given-names></name><name><surname>Schell</surname><given-names>H.</given-names></name><name><surname>Kahle</surname><given-names>P.J.</given-names></name><etal></etal></person-group><article-title>Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice</article-title><source>Neurobiol. Dis.</source><year>2014</year><volume>69</volume><fpage>134</fpage><lpage>143</lpage><pub-id pub-id-type="doi">10.1016/j.nbd.2014.05.009</pub-id><pub-id pub-id-type="pmid">24851801</pub-id></element-citation></ref><ref id="B49-biomolecules-05-01122"><label>49.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lavedan</surname><given-names>C.</given-names></name></person-group><article-title>The synuclein family</article-title><source>Genome Res.</source><year>1998</year><volume>8</volume><fpage>871</fpage><lpage>880</lpage><pub-id pub-id-type="pmid">9750188</pub-id></element-citation></ref><ref id="B50-biomolecules-05-01122"><label>50.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maroteaux</surname><given-names>L.</given-names></name><name><surname>Campanelli</surname><given-names>J.T.</given-names></name><name><surname>Scheller</surname><given-names>R.H.</given-names></name></person-group><article-title>Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal</article-title><source>J. Neurosci.</source><year>1988</year><volume>8</volume><fpage>2804</fpage><lpage>2815</lpage><pub-id pub-id-type="pmid">3411354</pub-id></element-citation></ref><ref id="B51-biomolecules-05-01122"><label>51.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bendor</surname><given-names>J.T.</given-names></name><name><surname>Logan</surname><given-names>T.P.</given-names></name><name><surname>Edwards</surname><given-names>R.H.</given-names></name></person-group><article-title>The function of α-synuclein</article-title><source>Neuron</source><year>2013</year><volume>79</volume><fpage>1044</fpage><lpage>1066</lpage><pub-id pub-id-type="doi">10.1016/j.neuron.2013.09.004</pub-id><pub-id pub-id-type="pmid">24050397</pub-id></element-citation></ref><ref id="B52-biomolecules-05-01122"><label>52.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>George</surname><given-names>J.M.</given-names></name></person-group><article-title>The synucleins</article-title><source>Genome Biol.</source><year>2002</year><pub-id pub-id-type="doi">10.1186/gb-2001-3-1-reviews3002</pub-id></element-citation></ref><ref id="B53-biomolecules-05-01122"><label>53.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bartels</surname><given-names>T.</given-names></name><name><surname>Choi</surname><given-names>J.G.</given-names></name><name><surname>Selkoe</surname><given-names>D.J.</given-names></name></person-group><article-title>α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation</article-title><source>Nature</source><year>2011</year><volume>477</volume><fpage>107</fpage><lpage>110</lpage><pub-id pub-id-type="doi">10.1038/nature10324</pub-id><pub-id pub-id-type="pmid">21841800</pub-id></element-citation></ref><ref id="B54-biomolecules-05-01122"><label>54.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>W.</given-names></name><name><surname>Perovic</surname><given-names>I.</given-names></name><name><surname>Chittuluru</surname><given-names>J.</given-names></name><name><surname>Kaganovich</surname><given-names>A.</given-names></name><name><surname>Nguyen</surname><given-names>L.T.</given-names></name><name><surname>Liao</surname><given-names>J.</given-names></name><name><surname>Auclair</surname><given-names>J.R.</given-names></name><name><surname>Johnson</surname><given-names>D.</given-names></name><name><surname>Landeru</surname><given-names>A.</given-names></name><name><surname>Simorellis</surname><given-names>A.K.</given-names></name><etal></etal></person-group><article-title>A soluble alpha-synuclein construct forms a dynamic tetramer</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2011</year><volume>108</volume><fpage>17797</fpage><lpage>17802</lpage><pub-id pub-id-type="doi">10.1073/pnas.1113260108</pub-id><pub-id pub-id-type="pmid">22006323</pub-id></element-citation></ref><ref id="B55-biomolecules-05-01122"><label>55.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Conway</surname><given-names>K.A.</given-names></name><name><surname>Lee</surname><given-names>S.J.</given-names></name><name><surname>Rochet</surname><given-names>J.C.</given-names></name><name><surname>Ding</surname><given-names>T.T.</given-names></name><name><surname>Harper</surname><given-names>J.D.</given-names></name><name><surname>Williamson</surname><given-names>R.E.</given-names></name><name><surname>Lansbury</surname><given-names>P.T.</given-names></name></person-group><article-title>Accelerated oligomerization by Parkinson’s disease linked α-synuclein mutants</article-title><source>Ann. NY Acad. Sci.</source><year>2000</year><volume>920</volume><fpage>42</fpage><lpage>45</lpage><pub-id pub-id-type="doi">10.1111/j.1749-6632.2000.tb06903.x</pub-id><pub-id pub-id-type="pmid">11193175</pub-id></element-citation></ref><ref id="B56-biomolecules-05-01122"><label>56.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Conway</surname><given-names>K.A.</given-names></name><name><surname>Rochet</surname><given-names>J.C.</given-names></name><name><surname>Bieganski</surname><given-names>R.M.</given-names></name><name><surname>Lansbury</surname><given-names>P.T.</given-names><suffix>Jr.</suffix></name></person-group><article-title>Kinetic stabilization of the α-synuclein protofibril by a dopamine—α-Synuclein adduct</article-title><source>Science</source><year>2001</year><volume>294</volume><fpage>1346</fpage><lpage>1349</lpage><pub-id pub-id-type="doi">10.1126/science.1063522</pub-id><pub-id pub-id-type="pmid">11701929</pub-id></element-citation></ref><ref id="B57-biomolecules-05-01122"><label>57.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fujiwara</surname><given-names>H.</given-names></name><name><surname>Hasegawa</surname><given-names>M.</given-names></name><name><surname>Dohmae</surname><given-names>N.</given-names></name><name><surname>Kawashima</surname><given-names>A.</given-names></name><name><surname>Masliah</surname><given-names>E.</given-names></name><name><surname>Goldberg</surname><given-names>M.S.</given-names></name><name><surname>Shen</surname><given-names>J.</given-names></name><name><surname>Takio</surname><given-names>K.</given-names></name><name><surname>Iwatsubo</surname><given-names>T.</given-names></name></person-group><article-title>α-Synuclein is phosphorylated in synucleinopathy lesions</article-title><source>Nat. Cell Biol.</source><year>2002</year><volume>4</volume><fpage>160</fpage><lpage>164</lpage><pub-id pub-id-type="pmid">11813001</pub-id></element-citation></ref><ref id="B58-biomolecules-05-01122"><label>58.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jethva</surname><given-names>P.N.</given-names></name><name><surname>Kardani</surname><given-names>J.R.</given-names></name><name><surname>Roy</surname><given-names>I.</given-names></name></person-group><article-title>Modulation of α-synuclein aggregation by dopamine in the presence of MPTP and its metabolite</article-title><source>FEBS J.</source><year>2011</year><volume>278</volume><fpage>1688</fpage><lpage>1698</lpage><pub-id pub-id-type="doi">10.1111/j.1742-4658.2011.08093.x</pub-id><pub-id pub-id-type="pmid">21410644</pub-id></element-citation></ref><ref id="B59-biomolecules-05-01122"><label>59.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jenco</surname><given-names>J.M.</given-names></name><name><surname>Rawlingson</surname><given-names>A.</given-names></name><name><surname>Daniels</surname><given-names>B.</given-names></name><name><surname>Morris</surname><given-names>A.J.</given-names></name></person-group><article-title>Regulation of phospholipase D2: Selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins</article-title><source>Biochemistry</source><year>1998</year><volume>37</volume><fpage>4901</fpage><lpage>4909</lpage><pub-id pub-id-type="doi">10.1021/bi972776r</pub-id><pub-id pub-id-type="pmid">9538008</pub-id></element-citation></ref><ref id="B60-biomolecules-05-01122"><label>60.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murphy</surname><given-names>D.D.</given-names></name><name><surname>Rueter</surname><given-names>S.M.</given-names></name><name><surname>Trojanowski</surname><given-names>J.Q.</given-names></name><name><surname>Lee</surname><given-names>V.M.</given-names></name></person-group><article-title>Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons</article-title><source>J. Neurosci.</source><year>2000</year><volume>20</volume><fpage>3214</fpage><lpage>3220</lpage><pub-id pub-id-type="pmid">10777786</pub-id></element-citation></ref><ref id="B61-biomolecules-05-01122"><label>61.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cabin</surname><given-names>D.E.</given-names></name><name><surname>Shimazu</surname><given-names>K.</given-names></name><name><surname>Murphy</surname><given-names>D.</given-names></name><name><surname>Cole</surname><given-names>N.B.</given-names></name><name><surname>Gottschalk</surname><given-names>W.</given-names></name><name><surname>McIlwain</surname><given-names>K.L.</given-names></name><name><surname>Orrison</surname><given-names>B.</given-names></name><name><surname>Chen</surname><given-names>A.</given-names></name><name><surname>Ellis</surname><given-names>C.E.</given-names></name><name><surname>Paylor</surname><given-names>R.</given-names></name><etal></etal></person-group><article-title>Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein</article-title><source>J. Neurosci.</source><year>2002</year><volume>22</volume><fpage>8797</fpage><lpage>8807</lpage><pub-id pub-id-type="pmid">12388586</pub-id></element-citation></ref><ref id="B62-biomolecules-05-01122"><label>62.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chandra</surname><given-names>S.</given-names></name><name><surname>Fornai</surname><given-names>F.</given-names></name><name><surname>Kwon</surname><given-names>H.B.</given-names></name><name><surname>Yazdani</surname><given-names>U.</given-names></name><name><surname>Atasoy</surname><given-names>D.</given-names></name><name><surname>Liu</surname><given-names>X.</given-names></name><name><surname>Hammer</surname><given-names>R.E.</given-names></name><name><surname>Battaglia</surname><given-names>G.</given-names></name><name><surname>German</surname><given-names>D.C.</given-names></name><name><surname>Castillo</surname><given-names>P.E.</given-names></name><etal></etal></person-group><article-title>Double-knockout mice for alpha- and beta-synucleins: Effect on synaptic functions</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2004</year><volume>101</volume><fpage>14966</fpage><lpage>14971</lpage><pub-id pub-id-type="doi">10.1073/pnas.0406283101</pub-id><pub-id pub-id-type="pmid">15465911</pub-id></element-citation></ref><ref id="B63-biomolecules-05-01122"><label>63.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>R.H.</given-names></name><name><surname>Wislet-Gendebien</surname><given-names>S.</given-names></name><name><surname>Samuel</surname><given-names>F.</given-names></name><name><surname>Visanji</surname><given-names>N.P.</given-names></name><name><surname>Zhang</surname><given-names>G.</given-names></name><name><surname>Marsilio</surname><given-names>D.</given-names></name><name><surname>Langman</surname><given-names>T.</given-names></name><name><surname>Fraser</surname><given-names>P.E.</given-names></name><name><surname>Tandon</surname><given-names>A.</given-names></name></person-group><article-title>α-Synuclein membrane association is regulated by the Rab3a recycling machinery and presynaptic activity</article-title><source>J. Biol. Chem.</source><year>2013</year><volume>288</volume><fpage>7438</fpage><lpage>7449</lpage><pub-id pub-id-type="doi">10.1074/jbc.M112.439497</pub-id><pub-id pub-id-type="pmid">23344955</pub-id></element-citation></ref><ref id="B64-biomolecules-05-01122"><label>64.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martin</surname><given-names>L.J.</given-names></name><name><surname>Pan</surname><given-names>Y.</given-names></name><name><surname>Price</surname><given-names>A.C.</given-names></name><name><surname>Sterling</surname><given-names>W.</given-names></name><name><surname>Copeland</surname><given-names>N.G.</given-names></name><name><surname>Jenkins</surname><given-names>N.A.</given-names></name><name><surname>Price</surname><given-names>D.L.</given-names></name><name><surname>Lee</surname><given-names>M.K.</given-names></name></person-group><article-title>Parkinson’s disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death</article-title><source>J. Neurosci.</source><year>2006</year><volume>26</volume><fpage>41</fpage><lpage>50</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.4308-05.2006</pub-id><pub-id pub-id-type="pmid">16399671</pub-id></element-citation></ref><ref id="B65-biomolecules-05-01122"><label>65.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Devi</surname><given-names>L.</given-names></name><name><surname>Raghavendran</surname><given-names>V.</given-names></name><name><surname>Prabhu</surname><given-names>B.M.</given-names></name><name><surname>Avadhani</surname><given-names>N.G.</given-names></name><name><surname>Anandatheerthavarada</surname><given-names>H.K.</given-names></name></person-group><article-title>Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain</article-title><source>J. Biol. Chem.</source><year>2008</year><volume>283</volume><fpage>9089</fpage><lpage>9100</lpage><pub-id pub-id-type="doi">10.1074/jbc.M710012200</pub-id><pub-id pub-id-type="pmid">18245082</pub-id></element-citation></ref><ref id="B66-biomolecules-05-01122"><label>66.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>G.</given-names></name><name><surname>Zhang</surname><given-names>C.</given-names></name><name><surname>Yin</surname><given-names>J.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name><name><surname>Cheng</surname><given-names>F.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Yang</surname><given-names>H.</given-names></name><name><surname>Uéda</surname><given-names>K.</given-names></name><name><surname>Chan</surname><given-names>P.</given-names></name><name><surname>Yu</surname><given-names>S.</given-names></name></person-group><article-title>alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity</article-title><source>Neurosci. Lett.</source><year>2009</year><volume>454</volume><fpage>187</fpage><lpage>192</lpage><pub-id pub-id-type="doi">10.1016/j.neulet.2009.02.056</pub-id><pub-id pub-id-type="pmid">19429081</pub-id></element-citation></ref><ref id="B67-biomolecules-05-01122"><label>67.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chinta</surname><given-names>S.J.</given-names></name><name><surname>Mallajosyula</surname><given-names>J.K.</given-names></name><name><surname>Rane</surname><given-names>A.</given-names></name><name><surname>Andersen</surname><given-names>J.K.</given-names></name></person-group><article-title>Mitochondrial α-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy <italic>in vivo</italic></article-title><source>Neurosci. Lett.</source><year>2010</year><volume>486</volume><fpage>235</fpage><lpage>239</lpage><pub-id pub-id-type="doi">10.1016/j.neulet.2010.09.061</pub-id><pub-id pub-id-type="pmid">20887775</pub-id></element-citation></ref><ref id="B68-biomolecules-05-01122"><label>68.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nakamura</surname><given-names>K.</given-names></name><name><surname>Nemani</surname><given-names>V.M.</given-names></name><name><surname>Azarbal</surname><given-names>F.</given-names></name><name><surname>Skibinski</surname><given-names>G.</given-names></name><name><surname>Levy</surname><given-names>J.M.</given-names></name><name><surname>Egami</surname><given-names>K.</given-names></name><name><surname>Munishkina</surname><given-names>L.</given-names></name><name><surname>Zhang</surname><given-names>J.</given-names></name><name><surname>Gardner</surname><given-names>B.</given-names></name><name><surname>Wakabayashi</surname><given-names>J.</given-names></name><etal></etal></person-group><article-title>Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein</article-title><source>J. Biol. Chem.</source><year>2011</year><volume>286</volume><fpage>20710</fpage><lpage>20726</lpage><pub-id pub-id-type="doi">10.1074/jbc.M110.213538</pub-id><pub-id pub-id-type="pmid">21489994</pub-id></element-citation></ref><ref id="B69-biomolecules-05-01122"><label>69.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cooper</surname><given-names>A.A.</given-names></name><name><surname>Gitler</surname><given-names>A.D.</given-names></name><name><surname>Cashikar</surname><given-names>A.</given-names></name><name><surname>Haynes</surname><given-names>C.M.</given-names></name><name><surname>Hill</surname><given-names>K.J.</given-names></name><name><surname>Bhullar</surname><given-names>B.</given-names></name><name><surname>Liu</surname><given-names>K.</given-names></name><name><surname>Xu</surname><given-names>K.</given-names></name><name><surname>Strathearn</surname><given-names>K.E.</given-names></name><name><surname>Liu</surname><given-names>F.</given-names></name><etal></etal></person-group><article-title>Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson’s models</article-title><source>Science</source><year>2006</year><volume>313</volume><fpage>324</fpage><lpage>328</lpage><pub-id pub-id-type="doi">10.1126/science.1129462</pub-id><pub-id pub-id-type="pmid">16794039</pub-id></element-citation></ref><ref id="B70-biomolecules-05-01122"><label>70.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gitler</surname><given-names>A.D.</given-names></name><name><surname>Bevis</surname><given-names>B.J.</given-names></name><name><surname>Shorter</surname><given-names>J.</given-names></name><name><surname>Strathearn</surname><given-names>K.E.</given-names></name><name><surname>Hamamichi</surname><given-names>S.</given-names></name><name><surname>Su</surname><given-names>L.J.</given-names></name><name><surname>Caldwell</surname><given-names>K.A.</given-names></name><name><surname>Caldwell</surname><given-names>G.A.</given-names></name><name><surname>Rochet</surname><given-names>J.C.</given-names></name><name><surname>McCaffery</surname><given-names>J.M.</given-names></name><etal></etal></person-group><article-title>The Parkinson’s disease protein alpha-synuclein disrupts cellular Rab homeostasis</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2008</year><volume>105</volume><fpage>145</fpage><lpage>150</lpage><pub-id pub-id-type="doi">10.1073/pnas.0710685105</pub-id><pub-id pub-id-type="pmid">18162536</pub-id></element-citation></ref><ref id="B71-biomolecules-05-01122"><label>71.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thayanidhi</surname><given-names>N.</given-names></name><name><surname>Helm</surname><given-names>J.R.</given-names></name><name><surname>Nycz</surname><given-names>D.C.</given-names></name><name><surname>Bentley</surname><given-names>M.</given-names></name><name><surname>Liang</surname><given-names>Y.</given-names></name><name><surname>Hay</surname><given-names>J.C.</given-names></name></person-group><article-title>Alpha-synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs</article-title><source>Mol. Biol. Cell.</source><year>2010</year><volume>21</volume><fpage>1850</fpage><lpage>1863</lpage><pub-id pub-id-type="doi">10.1091/mbc.E09-09-0801</pub-id><pub-id pub-id-type="pmid">20392839</pub-id></element-citation></ref><ref id="B72-biomolecules-05-01122"><label>72.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ebrahimi-Fakhari</surname><given-names>D.</given-names></name><name><surname>Cantuti-Castelvetri</surname><given-names>I.</given-names></name><name><surname>Fan</surname><given-names>Z.</given-names></name><name><surname>Rockenstein</surname><given-names>E.</given-names></name><name><surname>Masliah</surname><given-names>E.</given-names></name><name><surname>Hyman</surname><given-names>B.T.</given-names></name><name><surname>McLean</surname><given-names>P.J.</given-names></name><name><surname>Unni</surname><given-names>V.K.</given-names></name></person-group><article-title>Distinct roles <italic>in vivo</italic> for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of α-synuclein</article-title><source>J. Neurosci.</source><year>2011</year><volume>31</volume><fpage>14508</fpage><lpage>14520</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.1560-11.2011</pub-id><pub-id pub-id-type="pmid">21994367</pub-id></element-citation></ref><ref id="B73-biomolecules-05-01122"><label>73.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Volles</surname><given-names>M.J.</given-names></name><name><surname>Lee</surname><given-names>S.J.</given-names></name><name><surname>Rochet</surname><given-names>J.C.</given-names></name><name><surname>Shtilerman</surname><given-names>M.D.</given-names></name><name><surname>Ding</surname><given-names>T.T.</given-names></name><name><surname>Kessler</surname><given-names>J.C.</given-names></name><name><surname>Lansbury</surname><given-names>P.T.</given-names><suffix>Jr.</suffix></name></person-group><article-title>Vesicle permeabilization by protofibrillar alpha-synuclein: Implications for the pathogenesis and treatment of Parkinson’s disease</article-title><source>Biochemistry</source><year>2001</year><volume>40</volume><fpage>7812</fpage><lpage>7819</lpage><pub-id pub-id-type="doi">10.1021/bi0102398</pub-id><pub-id pub-id-type="pmid">11425308</pub-id></element-citation></ref><ref id="B74-biomolecules-05-01122"><label>74.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dias</surname><given-names>V.</given-names></name><name><surname>Junn</surname><given-names>E.</given-names></name><name><surname>Mouradian</surname><given-names>M.M.</given-names></name></person-group><article-title>The role of oxidative stress in Parkinson’s disease</article-title><source>J. Park. Dis.</source><year>2013</year><volume>3</volume><fpage>461</fpage><lpage>491</lpage></element-citation></ref><ref id="B75-biomolecules-05-01122"><label>75.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oueslati</surname><given-names>A.</given-names></name><name><surname>Ximerakis</surname><given-names>M.</given-names></name><name><surname>Vekrellis</surname><given-names>K.</given-names></name></person-group><article-title>Protein transmission, seeding and degradation: key steps for α-synuclein prion-like propagation</article-title><source>Exp. Neurobiol.</source><year>2014</year><volume>23</volume><fpage>324</fpage><lpage>336</lpage><pub-id pub-id-type="doi">10.5607/en.2014.23.4.324</pub-id><pub-id pub-id-type="pmid">25548532</pub-id></element-citation></ref><ref id="B76-biomolecules-05-01122"><label>76.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Surgucheva</surname><given-names>I.</given-names></name><name><surname>Newell</surname><given-names>K.L.</given-names></name><name><surname>Burns</surname><given-names>J.</given-names></name><name><surname>Surguchov</surname><given-names>A.</given-names></name></person-group><article-title>New α- and γ-synuclein immunopathological lesions in human brain</article-title><source>Acta Neuropathol Commun.</source><year>2014</year><pub-id pub-id-type="doi">10.1186/s40478-014-0132-8</pub-id><pub-id pub-id-type="pmid">25209836</pub-id></element-citation></ref><ref id="B77-biomolecules-05-01122"><label>77.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Anderson</surname><given-names>J.P.</given-names></name><name><surname>Walker</surname><given-names>D.E.</given-names></name><name><surname>Goldstein</surname><given-names>J.M.</given-names></name><name><surname>de Laat</surname><given-names>R.</given-names></name><name><surname>Banducci</surname><given-names>K.</given-names></name><name><surname>Caccavello</surname><given-names>R.J.</given-names></name><name><surname>Barbour</surname><given-names>R.</given-names></name><name><surname>Huang</surname><given-names>J.</given-names></name><name><surname>Kling</surname><given-names>K.</given-names></name><name><surname>Lee</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease</article-title><source>J. Biol. Chem.</source><year>2006</year><volume>281</volume><fpage>29739</fpage><lpage>29752</lpage><pub-id pub-id-type="doi">10.1074/jbc.M600933200</pub-id><pub-id pub-id-type="pmid">16847063</pub-id></element-citation></ref><ref id="B78-biomolecules-05-01122"><label>78.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kahle</surname><given-names>P.J.</given-names></name><name><surname>Neumann</surname><given-names>M.</given-names></name><name><surname>Ozmen</surname><given-names>L.</given-names></name><name><surname>Muller</surname><given-names>V.</given-names></name><name><surname>Jacobsen</surname><given-names>H.</given-names></name><name><surname>Schindzielorz</surname><given-names>A.</given-names></name><name><surname>Okochi</surname><given-names>M.</given-names></name><name><surname>Leimer</surname><given-names>U.</given-names></name><name><surname>van der Putten</surname><given-names>H.</given-names></name><name><surname>Probst</surname><given-names>A.</given-names></name><etal></etal></person-group><article-title>Subcellular localization of wild-type and Parkinson’s disease-associated mutant alpha-synuclein in human and transgenic mouse brain</article-title><source>J. Neurosci.</source><year>2000</year><volume>20</volume><fpage>6365</fpage><lpage>6373</lpage><pub-id pub-id-type="pmid">10964942</pub-id></element-citation></ref><ref id="B79-biomolecules-05-01122"><label>79.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takahashi</surname><given-names>T.</given-names></name><name><surname>Yamashita</surname><given-names>H.</given-names></name><name><surname>Nagano</surname><given-names>Y.</given-names></name><name><surname>Nakamura</surname><given-names>T.</given-names></name><name><surname>Ohmori</surname><given-names>H.</given-names></name><name><surname>Avraham</surname><given-names>H.</given-names></name><name><surname>Avraham</surname><given-names>S.</given-names></name><name><surname>Yasuda</surname><given-names>M.</given-names></name><name><surname>Matsumoto</surname><given-names>M.</given-names></name></person-group><article-title>Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation</article-title><source>J. Biol. Chem.</source><year>2003</year><volume>278</volume><fpage>42225</fpage><lpage>42233</lpage><pub-id pub-id-type="doi">10.1074/jbc.M213217200</pub-id><pub-id pub-id-type="pmid">12893833</pub-id></element-citation></ref><ref id="B80-biomolecules-05-01122"><label>80.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Azeredo da Silveira</surname><given-names>S.</given-names></name><name><surname>Schneider</surname><given-names>B.L.</given-names></name><name><surname>Cifuentes-Diaz</surname><given-names>C.</given-names></name><name><surname>Sage</surname><given-names>D.</given-names></name><name><surname>Abbas-Terki</surname><given-names>T.</given-names></name><name><surname>Iwatsubo</surname><given-names>T.</given-names></name><name><surname>Unser</surname><given-names>M.</given-names></name><name><surname>Aebischer</surname><given-names>P.</given-names></name></person-group><article-title>Phosphorylation does not prompt, nor prevent, the formation of α-synuclein toxic species in a rat model of Parkinson’s disease</article-title><source>Hum. Mol. Genet.</source><year>2009</year><volume>18</volume><fpage>872</fpage><lpage>887</lpage><pub-id pub-id-type="pmid">19074459</pub-id></element-citation></ref><ref id="B81-biomolecules-05-01122"><label>81.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McFarland</surname><given-names>N.R.</given-names></name><name><surname>Fan</surname><given-names>Z.</given-names></name><name><surname>Xu</surname><given-names>K.</given-names></name><name><surname>Schwarzschild</surname><given-names>M.A.</given-names></name><name><surname>Feany</surname><given-names>M.B.</given-names></name><name><surname>Hyman</surname><given-names>B.T.</given-names></name><name><surname>McLean</surname><given-names>P.J.</given-names></name></person-group><article-title>Alpha-synuclein S129 phosphorylation mutants do not alter nigrostriatal toxicity in a rat model of Parkinson disease</article-title><source>J. Neuropathol. Exp. Neurol.</source><year>2009</year><volume>68</volume><fpage>515</fpage><lpage>524</lpage><pub-id pub-id-type="doi">10.1097/NEN.0b013e3181a24b53</pub-id><pub-id pub-id-type="pmid">19525899</pub-id></element-citation></ref><ref id="B82-biomolecules-05-01122"><label>82.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sato</surname><given-names>H.</given-names></name><name><surname>Kato</surname><given-names>T.</given-names></name><name><surname>Arawaka</surname><given-names>S.</given-names></name></person-group><article-title>The role of Ser129 phosphorylation of α-synuclein in neurodegeneration of Parkinson’s disease: Areview of <italic>in vivo</italic> models</article-title><source>Rev. Neurosci.</source><year>2013</year><volume>24</volume><fpage>115</fpage><lpage>123</lpage><pub-id pub-id-type="doi">10.1515/revneuro-2012-0071</pub-id><pub-id pub-id-type="pmid">23314528</pub-id></element-citation></ref><ref id="B83-biomolecules-05-01122"><label>83.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Waxman</surname><given-names>E.A.</given-names></name><name><surname>Giasson</surname><given-names>B.I.</given-names></name></person-group><article-title>Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein</article-title><source>J. Neuropathol. Exp. Neurol.</source><year>2008</year><volume>67</volume><fpage>402</fpage><lpage>416</lpage><pub-id pub-id-type="doi">10.1097/NEN.0b013e3186fc995</pub-id><pub-id pub-id-type="pmid">18451726</pub-id></element-citation></ref><ref id="B84-biomolecules-05-01122"><label>84.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mbefo</surname><given-names>M.K.</given-names></name><name><surname>Paleologou</surname><given-names>K.E.</given-names></name><name><surname>Boucharaba</surname><given-names>A.</given-names></name><name><surname>Oueslati</surname><given-names>A.</given-names></name><name><surname>Schell</surname><given-names>H.</given-names></name><name><surname>Fournier</surname><given-names>M.</given-names></name><name><surname>Olschewski</surname><given-names>D.</given-names></name><name><surname>Yin</surname><given-names>G.</given-names></name><name><surname>Zweckstetter</surname><given-names>M.</given-names></name><name><surname>Masliah</surname><given-names>E.</given-names></name><etal></etal></person-group><article-title>Phosphorylation of synucleins by members of the Polo-like kinase family</article-title><source>J. Biol. Chem.</source><year>2010</year><volume>285</volume><fpage>2807</fpage><lpage>2822</lpage><pub-id pub-id-type="doi">10.1074/jbc.M109.081950</pub-id><pub-id pub-id-type="pmid">19889641</pub-id></element-citation></ref><ref id="B85-biomolecules-05-01122"><label>85.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Waxman</surname><given-names>E.A.</given-names></name><name><surname>Giasson</surname><given-names>B.I.</given-names></name></person-group><article-title>Induction of intracellular tau aggregation is promoted by α-synuclein seeds and provides novel insights into the hyperphosphorylation of tau</article-title><source>J. Neurosci.</source><year>2011</year><volume>31</volume><fpage>7604</fpage><lpage>7618</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.0297-11.2011</pub-id><pub-id pub-id-type="pmid">21613474</pub-id></element-citation></ref><ref id="B86-biomolecules-05-01122"><label>86.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tenreiro</surname><given-names>S.</given-names></name><name><surname>Eckermann</surname><given-names>K.</given-names></name><name><surname>Outeiro</surname><given-names>T.F.</given-names></name></person-group><article-title>Protein phosphorylation in neurodegeneration: Friend or foe?</article-title><source>Front. Mol. Neurosci.</source><year>2014</year><pub-id pub-id-type="doi">10.3389/fnmol.2014.00042</pub-id><pub-id pub-id-type="pmid">24860424</pub-id></element-citation></ref><ref id="B87-biomolecules-05-01122"><label>87.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oueslati</surname><given-names>A.</given-names></name><name><surname>Schneider</surname><given-names>B.L.</given-names></name><name><surname>Aebischer</surname><given-names>P.</given-names></name><name><surname>Lashuel</surname><given-names>H.A.</given-names></name></person-group><article-title>Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity <italic>in vivo</italic></article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2013</year><volume>110</volume><fpage>E3945</fpage><lpage>E3954</lpage><pub-id pub-id-type="doi">10.1073/pnas.1309991110</pub-id><pub-id pub-id-type="pmid">23983262</pub-id></element-citation></ref><ref id="B88-biomolecules-05-01122"><label>88.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rott</surname><given-names>R.</given-names></name><name><surname>Szargel</surname><given-names>R.</given-names></name><name><surname>Shani</surname><given-names>V.</given-names></name><name><surname>Bisharat</surname><given-names>S.</given-names></name><name><surname>Engelender</surname><given-names>S.</given-names></name></person-group><article-title>α-Synuclein ubiquitination and novel therapeutic targets for Parkinson’s disease</article-title><source>CNS Neurol. Disord. Drug Targets</source><year>2014</year><volume>13</volume><fpage>630</fpage><lpage>637</lpage><pub-id pub-id-type="doi">10.2174/18715273113126660195</pub-id><pub-id pub-id-type="pmid">24168368</pub-id></element-citation></ref><ref id="B89-biomolecules-05-01122"><label>89.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Haj-Yahya</surname><given-names>M.</given-names></name><name><surname>Fauvet</surname><given-names>B.</given-names></name><name><surname>Herman-Bachinsky</surname><given-names>Y.</given-names></name><name><surname>Hejjaoui</surname><given-names>M.</given-names></name><name><surname>Bavikar</surname><given-names>S.N.</given-names></name><name><surname>Karthikeyan</surname><given-names>S.V.</given-names></name><name><surname>Ciechanover</surname><given-names>A.</given-names></name><name><surname>Lashuel</surname><given-names>H.A.</given-names></name><name><surname>Brik</surname><given-names>A.</given-names></name></person-group><article-title>Synthetic polyubiquitinated α-synuclein reveals important insights into the roles of the ubiquitin chain in regulating its pathophysiology</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2013</year><volume>110</volume><fpage>17726</fpage><lpage>17731</lpage><pub-id pub-id-type="doi">10.1073/pnas.1315654110</pub-id><pub-id pub-id-type="pmid">24043770</pub-id></element-citation></ref><ref id="B90-biomolecules-05-01122"><label>90.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tofaris</surname><given-names>G.K.</given-names></name><name><surname>Garcia Reitböck</surname><given-names>P.</given-names></name><name><surname>Humby</surname><given-names>T.</given-names></name><name><surname>Lambourne</surname><given-names>S.L.</given-names></name><name><surname>O’Connell</surname><given-names>M.</given-names></name><name><surname>Ghetti</surname><given-names>B.</given-names></name><name><surname>Gossage</surname><given-names>H.</given-names></name><name><surname>Emson</surname><given-names>P.C.</given-names></name><name><surname>Wilkinson</surname><given-names>L.S.</given-names></name><name><surname>Goedert</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human α-synuclein (1–120): Implications for Lewy body disorders</article-title><source>J. Neurosci.</source><year>2006</year><volume>26</volume><fpage>3942</fpage><lpage>3950</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.4965-05.2006</pub-id><pub-id pub-id-type="pmid">16611810</pub-id></element-citation></ref><ref id="B91-biomolecules-05-01122"><label>91.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Souza</surname><given-names>J.M.</given-names></name><name><surname>Giasson</surname><given-names>B.I.</given-names></name><name><surname>Chen</surname><given-names>Q.</given-names></name><name><surname>Lee</surname><given-names>V.M.</given-names></name><name><surname>Ischiropoulos</surname><given-names>H.</given-names></name></person-group><article-title>Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies</article-title><source>J. Biol. Chem.</source><year>2000</year><volume>275</volume><fpage>18344</fpage><lpage>18349</lpage><pub-id pub-id-type="doi">10.1074/jbc.M000206200</pub-id><pub-id pub-id-type="pmid">10747881</pub-id></element-citation></ref><ref id="B92-biomolecules-05-01122"><label>92.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vila</surname><given-names>M.</given-names></name><name><surname>Vukosavic</surname><given-names>S.</given-names></name><name><surname>Jackson-Lewis</surname><given-names>V.</given-names></name><name><surname>Neystat</surname><given-names>M.</given-names></name><name><surname>Jakowec</surname><given-names>M.</given-names></name><name><surname>Przedborski</surname><given-names>S.</given-names></name></person-group><article-title>α-Synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP</article-title><source>J. Neurochem.</source><year>2000</year><volume>74</volume><fpage>721</fpage><lpage>729</lpage><pub-id pub-id-type="doi">10.1046/j.1471-4159.2000.740721.x</pub-id><pub-id pub-id-type="pmid">10646524</pub-id></element-citation></ref><ref id="B93-biomolecules-05-01122"><label>93.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hsu</surname><given-names>L.J.</given-names></name><name><surname>Sagara</surname><given-names>Y.</given-names></name><name><surname>Arroyo</surname><given-names>A.</given-names></name><name><surname>Rockenstein</surname><given-names>E.</given-names></name><name><surname>Sisk</surname><given-names>A.</given-names></name><name><surname>Mallory</surname><given-names>M.</given-names></name><name><surname>Wong</surname><given-names>J.</given-names></name><name><surname>Takenouchi</surname><given-names>T.</given-names></name><name><surname>Hashimoto</surname><given-names>M.</given-names></name><name><surname>Masliah</surname><given-names>E.</given-names></name></person-group><article-title>Alpha-synuclein promotes mitochondrial deficit and oxidative stress</article-title><source>Am. J. Pathol.</source><year>2000</year><volume>157</volume><fpage>401</fpage><lpage>410</lpage><pub-id pub-id-type="doi">10.1016/S0002-9440(10)64553-1</pub-id><pub-id pub-id-type="pmid">10934145</pub-id></element-citation></ref><ref id="B94-biomolecules-05-01122"><label>94.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hashimoto</surname><given-names>M.</given-names></name><name><surname>Takeda</surname><given-names>A.</given-names></name><name><surname>Hsu</surname><given-names>L.J.</given-names></name><name><surname>Takenouchi</surname><given-names>T.</given-names></name><name><surname>Masliah</surname><given-names>E.</given-names></name></person-group><article-title>Role of cytochrome C as a stimulator of alpha-synuclein aggregation in Lewy body disease</article-title><source>J. Biol. Chem.</source><year>1999</year><volume>274</volume><fpage>28849</fpage><lpage>28852</lpage><pub-id pub-id-type="doi">10.1074/jbc.274.41.28849</pub-id><pub-id pub-id-type="pmid">10506125</pub-id></element-citation></ref><ref id="B95-biomolecules-05-01122"><label>95.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Levin</surname><given-names>J.</given-names></name><name><surname>Högen</surname><given-names>T.</given-names></name><name><surname>Hillmer</surname><given-names>A.S.</given-names></name><name><surname>Bader</surname><given-names>B.</given-names></name><name><surname>Schmidt</surname><given-names>F.</given-names></name><name><surname>Kamp</surname><given-names>F.</given-names></name><name><surname>Kretzschmar</surname><given-names>H.A.</given-names></name><name><surname>Bötzel</surname><given-names>K.</given-names></name><name><surname>Giese</surname><given-names>A.</given-names></name></person-group><article-title>Generation of ferric iron links oxidative stress to α-synuclein oligomer formation</article-title><source>J. Park. Dis.</source><year>2011</year><volume>1</volume><fpage>205</fpage><lpage>216</lpage><pub-id pub-id-type="doi">10.1016/j.baga.2011.01.007</pub-id></element-citation></ref><ref id="B96-biomolecules-05-01122"><label>96.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>K.S.</given-names></name><name><surname>Choi</surname><given-names>S.Y.</given-names></name><name><surname>Kwon</surname><given-names>H.Y.</given-names></name><name><surname>Won</surname><given-names>M.H.</given-names></name><name><surname>Kang</surname><given-names>T.C.</given-names></name><name><surname>Kang</surname><given-names>J.H.</given-names></name></person-group><article-title>Aggregation of α-synuclein induced by the Cu, Zn-superoxide dismutase and hydrogen peroxide system</article-title><source>Free Radic. Biol. Med.</source><year>2002</year><volume>32</volume><fpage>544</fpage><lpage>550</lpage><pub-id pub-id-type="doi">10.1016/S0891-5849(02)00741-4</pub-id><pub-id pub-id-type="pmid">11958955</pub-id></element-citation></ref><ref id="B97-biomolecules-05-01122"><label>97.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goers</surname><given-names>J.</given-names></name><name><surname>Manning-Bog</surname><given-names>A.B.</given-names></name><name><surname>McCormack</surname><given-names>A.L.</given-names></name><name><surname>Millett</surname><given-names>I.S.</given-names></name><name><surname>Doniach</surname><given-names>S.</given-names></name><name><surname>di Monte</surname><given-names>D.A.</given-names></name><name><surname>Uversky</surname><given-names>V.N.</given-names></name><name><surname>Fink</surname><given-names>A.L.</given-names></name></person-group><article-title>Nuclear localization of alpha-synuclein and its interaction with histones</article-title><source>Biochemistry</source><year>2003</year><volume>42</volume><fpage>8465</fpage><lpage>8471</lpage><pub-id pub-id-type="doi">10.1021/bi0341152</pub-id><pub-id pub-id-type="pmid">12859192</pub-id></element-citation></ref><ref id="B98-biomolecules-05-01122"><label>98.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>S.</given-names></name><name><surname>Zhou</surname><given-names>M.</given-names></name><name><surname>Yu</surname><given-names>S.</given-names></name><name><surname>Cai</surname><given-names>Y.</given-names></name><name><surname>Zhang</surname><given-names>A.</given-names></name><name><surname>Uéda</surname><given-names>K.</given-names></name><name><surname>Chan</surname><given-names>P.</given-names></name></person-group><article-title>Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells</article-title><source>Biochem. Biophys. Res. Commun.</source><year>2006</year><volume>342</volume><fpage>330</fpage><lpage>335</lpage><pub-id pub-id-type="doi">10.1016/j.bbrc.2006.01.148</pub-id><pub-id pub-id-type="pmid">16480958</pub-id></element-citation></ref><ref id="B99-biomolecules-05-01122"><label>99.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>M.</given-names></name><name><surname>Xu</surname><given-names>S.</given-names></name><name><surname>Mi</surname><given-names>J.</given-names></name><name><surname>Uéda</surname><given-names>K.</given-names></name><name><surname>Chan</surname><given-names>P.</given-names></name></person-group><article-title>Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress</article-title><source>Brain Res.</source><year>2013</year><volume>1500</volume><fpage>19</fpage><lpage>27</lpage><pub-id pub-id-type="doi">10.1016/j.brainres.2013.01.024</pub-id><pub-id pub-id-type="pmid">23337620</pub-id></element-citation></ref><ref id="B100-biomolecules-05-01122"><label>100.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hasegawa</surname><given-names>T.</given-names></name><name><surname>Matsuzaki-Kobayashi</surname><given-names>M.</given-names></name><name><surname>Takeda</surname><given-names>A.</given-names></name><name><surname>Sugeno</surname><given-names>N.</given-names></name><name><surname>Kikuchi</surname><given-names>A.</given-names></name><name><surname>Furukawa</surname><given-names>K.</given-names></name><name><surname>Perry</surname><given-names>G.</given-names></name><name><surname>Smith</surname><given-names>M.A.</given-names></name><name><surname>Itoyama</surname><given-names>Y.</given-names></name></person-group><article-title>Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: Implications for selective neurodegeneration in Parkinson’s disease</article-title><source>FEBS Lett.</source><year>2006</year><volume>580</volume><fpage>2147</fpage><lpage>2152</lpage><pub-id pub-id-type="doi">10.1016/j.febslet.2006.03.018</pub-id><pub-id pub-id-type="pmid">16567160</pub-id></element-citation></ref><ref id="B101-biomolecules-05-01122"><label>101.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yu</surname><given-names>S.</given-names></name><name><surname>Uéda</surname><given-names>K.</given-names></name><name><surname>Chan</surname><given-names>P.</given-names></name></person-group><article-title>α-Synuclein and dopamine metabolism</article-title><source>Mol. Neurobiol.</source><year>2005</year><volume>31</volume><fpage>243</fpage><lpage>254</lpage><pub-id pub-id-type="doi">10.1385/MN:31:1-3:243</pub-id><pub-id pub-id-type="pmid">15953825</pub-id></element-citation></ref><ref id="B102-biomolecules-05-01122"><label>102.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schlüter</surname><given-names>O.M.</given-names></name><name><surname>Fornai</surname><given-names>F.</given-names></name><name><surname>Alessandrí</surname><given-names>M.G.</given-names></name><name><surname>Takamori</surname><given-names>S.</given-names></name><name><surname>Geppert</surname><given-names>M.</given-names></name><name><surname>Jahn</surname><given-names>R.</given-names></name><name><surname>Südhof</surname><given-names>T.C.</given-names></name></person-group><article-title>Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice</article-title><source>Neuroscience</source><year>2003</year><volume>118</volume><fpage>985</fpage><lpage>1002</lpage><pub-id pub-id-type="doi">10.1016/S0306-4522(03)00036-8</pub-id><pub-id pub-id-type="pmid">12732244</pub-id></element-citation></ref><ref id="B103-biomolecules-05-01122"><label>103.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>M.</given-names></name><name><surname>Xu</surname><given-names>S.L.</given-names></name><name><surname>Chen</surname><given-names>B.</given-names></name></person-group><article-title>Dual effects of different concentrations of alpha-synuclein on the neurotoxicity of 6-hydroxydopamine in SH-SY5Y cells</article-title><source>Sheng Li Xue Bao</source><year>2009</year><volume>61</volume><fpage>324</fpage><lpage>330</lpage><pub-id pub-id-type="pmid">19701583</pub-id></element-citation></ref><ref id="B104-biomolecules-05-01122"><label>104.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thomas</surname><given-names>B.</given-names></name><name><surname>Mandir</surname><given-names>A.S.</given-names></name><name><surname>West</surname><given-names>N.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Andrabi</surname><given-names>S.A.</given-names></name><name><surname>Stirling</surname><given-names>W.</given-names></name><name><surname>Dawson</surname><given-names>V.L.</given-names></name><name><surname>Dawson</surname><given-names>T.M.</given-names></name><name><surname>Lee</surname><given-names>M.K.</given-names></name></person-group><article-title>Resistance to MPTP-neurotoxicity in α-synuclein knockout mice is complemented by human α-synuclein and associated with increased β-synuclein and Akt activation</article-title><source>PLoS ONE</source><year>2011</year><volume>6</volume><fpage>e16706</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0016706</pub-id><pub-id pub-id-type="pmid">21304957</pub-id></element-citation></ref><ref id="B105-biomolecules-05-01122"><label>105.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Klivenyi</surname><given-names>P.</given-names></name><name><surname>Siwek</surname><given-names>D.</given-names></name><name><surname>Gardian</surname><given-names>G.</given-names></name><name><surname>Yang</surname><given-names>L.</given-names></name><name><surname>Starkov</surname><given-names>A.</given-names></name><name><surname>Cleren</surname><given-names>C.</given-names></name><name><surname>Ferrante</surname><given-names>R.J.</given-names></name><name><surname>Kowall</surname><given-names>N.W.</given-names></name><name><surname>Abeliovich</surname><given-names>A.</given-names></name><name><surname>Beal</surname><given-names>M.F.</given-names></name></person-group><article-title>Mice lacking alpha-synuclein are resistant to mitochondrial toxins</article-title><source>Neurobiol. Dis.</source><year>2006</year><volume>21</volume><fpage>541</fpage><lpage>548</lpage><pub-id pub-id-type="doi">10.1016/j.nbd.2005.08.018</pub-id><pub-id pub-id-type="pmid">16298531</pub-id></element-citation></ref><ref id="B106-biomolecules-05-01122"><label>106.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Duffy</surname><given-names>P.E.</given-names></name><name><surname>Tennyson</surname><given-names>V.M.</given-names></name></person-group><article-title>Phase and electron microscopic observations of Lewy bodies and melanin granules in the substantia nigra and locus coeruleus in Parkinson’s disease</article-title><source>J. Neuropthol. Exp. Neurol.</source><year>1965</year><volume>24</volume><fpage>398</fpage><lpage>414</lpage><pub-id pub-id-type="doi">10.1097/00005072-196507000-00003</pub-id></element-citation></ref><ref id="B107-biomolecules-05-01122"><label>107.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fenichel</surname><given-names>G.M.</given-names></name><name><surname>Bazelon</surname><given-names>M.</given-names></name></person-group><article-title>Studies on neuromelanin. II. Melanin in the brainstems of infants and children</article-title><source>Neurology</source><year>1968</year><volume>18</volume><fpage>817</fpage><lpage>820</lpage><pub-id pub-id-type="doi">10.1212/WNL.18.8.817</pub-id><pub-id pub-id-type="pmid">5692344</pub-id></element-citation></ref><ref id="B108-biomolecules-05-01122"><label>108.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheng</surname><given-names>J.</given-names></name><name><surname>Moss</surname><given-names>S.C.</given-names></name><name><surname>Eisner</surname><given-names>M.</given-names></name></person-group><article-title>X-ray characterization of melanins–II</article-title><source>Pigment Cell Res.</source><year>1994</year><volume>7</volume><fpage>263</fpage><lpage>273</lpage><pub-id pub-id-type="doi">10.1111/j.1600-0749.1994.tb00061.x</pub-id><pub-id pub-id-type="pmid">7855075</pub-id></element-citation></ref><ref id="B109-biomolecules-05-01122"><label>109.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Haavik</surname><given-names>J.</given-names></name></person-group><article-title>L-DOPA is a substrate for tyrosine hydroxylase</article-title><source>J. Neurochem.</source><year>1997</year><volume>69</volume><fpage>1720</fpage><lpage>1728</lpage><pub-id pub-id-type="doi">10.1046/j.1471-4159.1997.69041720.x</pub-id><pub-id pub-id-type="pmid">9326301</pub-id></element-citation></ref><ref id="B110-biomolecules-05-01122"><label>110.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okun</surname><given-names>M.R.</given-names></name></person-group><article-title>The role of peroxidase in neuromelanin synthesis: A review</article-title><source>Physiol. Chem. Phys. Med. NMR</source><year>1997</year><volume>29</volume><fpage>15</fpage><lpage>22</lpage><pub-id pub-id-type="pmid">9353954</pub-id></element-citation></ref><ref id="B111-biomolecules-05-01122"><label>111.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sulzer</surname><given-names>D.</given-names></name><name><surname>Bogulavsky</surname><given-names>J.</given-names></name><name><surname>Larsen</surname><given-names>K.E.</given-names></name><name><surname>Behr</surname><given-names>G.</given-names></name><name><surname>Karatekin</surname><given-names>E.</given-names></name><name><surname>Kleinman</surname><given-names>M.H.</given-names></name><name><surname>Turro</surname><given-names>N.</given-names></name><name><surname>Krantz</surname><given-names>D.</given-names></name><name><surname>Edwards</surname><given-names>R.H.</given-names></name><name><surname>Greene</surname><given-names>L.A.</given-names></name><etal></etal></person-group><article-title>Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2000</year><volume>97</volume><fpage>11869</fpage><lpage>11874</lpage><pub-id pub-id-type="doi">10.1073/pnas.97.22.11869</pub-id><pub-id pub-id-type="pmid">11050221</pub-id></element-citation></ref><ref id="B112-biomolecules-05-01122"><label>112.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>D’Amato</surname><given-names>R.J.</given-names></name><name><surname>Lipman</surname><given-names>Z.P.</given-names></name><name><surname>Snyder</surname><given-names>S.H.</given-names></name></person-group><article-title>Selectivity of the parkinsonian neurotoxin MPTP: Toxic metabolite MPP+ binds to neuromelanin</article-title><source>Science</source><year>1986</year><volume>231</volume><fpage>987</fpage><lpage>989</lpage><pub-id pub-id-type="doi">10.1126/science.3080808</pub-id><pub-id pub-id-type="pmid">3080808</pub-id></element-citation></ref><ref id="B113-biomolecules-05-01122"><label>113.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lindquist</surname><given-names>N.G.</given-names></name><name><surname>Larsson</surname><given-names>B.S.</given-names></name><name><surname>Lydén-Sokolowski</surname><given-names>A.</given-names></name></person-group><article-title>Neuromelanin and its possible protective and destructive properties</article-title><source>Pigment Cell Res.</source><year>1987</year><volume>1</volume><fpage>133</fpage><lpage>136</lpage><pub-id pub-id-type="doi">10.1111/j.1600-0749.1987.tb00403.x</pub-id><pub-id pub-id-type="pmid">3334086</pub-id></element-citation></ref><ref id="B114-biomolecules-05-01122"><label>114.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Pietra</surname><given-names>R.</given-names></name><name><surname>Goj</surname><given-names>C.</given-names></name><name><surname>Mecacci</surname><given-names>C.</given-names></name><name><surname>Radice</surname><given-names>D.</given-names></name><name><surname>Sabbioni</surname><given-names>E.</given-names></name></person-group><article-title>Iron and other metals in neuromelanin, substantia nigra, and putamen of human brain</article-title><source>J. Neurochem.</source><year>1994</year><volume>62</volume><fpage>1097</fpage><lpage>1101</lpage><pub-id pub-id-type="doi">10.1046/j.1471-4159.1994.62031097.x</pub-id><pub-id pub-id-type="pmid">8113797</pub-id></element-citation></ref><ref id="B115-biomolecules-05-01122"><label>115.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fornstedt</surname><given-names>B.</given-names></name><name><surname>Brun</surname><given-names>A.</given-names></name><name><surname>Rosengren</surname><given-names>E.</given-names></name><name><surname>Carlsson</surname><given-names>A.</given-names></name></person-group><article-title>The apparent autoxidation rate of catechols in dopamine-rich regions of human brains increases with the degree of depigmentation of substantia nigra</article-title><source>J. Neural Transm. Park. Dis. Dement Sect.</source><year>1989</year><volume>1</volume><fpage>279</fpage><lpage>295</lpage><pub-id pub-id-type="doi">10.1007/BF02263482</pub-id><pub-id pub-id-type="pmid">2597314</pub-id></element-citation></ref><ref id="B116-biomolecules-05-01122"><label>116.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilczok</surname><given-names>T.</given-names></name><name><surname>Stepien</surname><given-names>K.</given-names></name><name><surname>Dzierzega-Lecznar</surname><given-names>A.</given-names></name><name><surname>Zajdel</surname><given-names>A.</given-names></name><name><surname>Wilczok</surname><given-names>A.</given-names></name></person-group><article-title>Model neuromelanins as antioxidative agents during lipid peroxidation</article-title><source>Neurotox. Res.</source><year>1999</year><volume>1</volume><fpage>141</fpage><lpage>147</lpage><pub-id pub-id-type="doi">10.1007/BF03033277</pub-id><pub-id pub-id-type="pmid">12835109</pub-id></element-citation></ref><ref id="B117-biomolecules-05-01122"><label>117.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shamoto-Nagai</surname><given-names>M.</given-names></name><name><surname>Maruyama</surname><given-names>W.</given-names></name><name><surname>Akao</surname><given-names>Y.</given-names></name><name><surname>Osawa</surname><given-names>T.</given-names></name><name><surname>Tribl</surname><given-names>F.</given-names></name><name><surname>Gerlach</surname><given-names>M.</given-names></name><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Riederer</surname><given-names>P.</given-names></name><name><surname>Naoi</surname><given-names>M.</given-names></name></person-group><article-title>Neuromelanin inhibits enzymatic activity of 26S proteasome in human dopaminergic SH-SY5Y cells</article-title><source>J. Neural Transm.</source><year>2004</year><volume>111</volume><fpage>1253</fpage><lpage>1265</lpage><pub-id pub-id-type="doi">10.1007/s00702-004-0211-2</pub-id><pub-id pub-id-type="pmid">15480837</pub-id></element-citation></ref><ref id="B118-biomolecules-05-01122"><label>118.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zareba</surname><given-names>M.</given-names></name><name><surname>Bober</surname><given-names>A.</given-names></name><name><surname>Korytowski</surname><given-names>W.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Sarna</surname><given-names>T.</given-names></name></person-group><article-title>The effect of a synthetic neruomelanin on yield of free hydroxyl radicals generated in model systems</article-title><source>Biochim. Biophys. Acta</source><year>1995</year><volume>1271</volume><fpage>343</fpage><lpage>348</lpage><pub-id pub-id-type="doi">10.1016/0925-4439(95)00058-C</pub-id><pub-id pub-id-type="pmid">7605801</pub-id></element-citation></ref><ref id="B119-biomolecules-05-01122"><label>119.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wakamatsu</surname><given-names>K.</given-names></name><name><surname>Fujikawa</surname><given-names>K.</given-names></name><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Ito</surname><given-names>S.</given-names></name></person-group><article-title>The structure of neuromelanin as studied by chemical degradative methods</article-title><source>J. Neurochem.</source><year>2003</year><volume>86</volume><fpage>1015</fpage><lpage>1023</lpage><pub-id pub-id-type="doi">10.1046/j.1471-4159.2003.01917.x</pub-id><pub-id pub-id-type="pmid">12887698</pub-id></element-citation></ref><ref id="B120-biomolecules-05-01122"><label>120.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ito</surname><given-names>S.</given-names></name><name><surname>Wakamatsu</surname><given-names>K.</given-names></name></person-group><article-title>Chemical degradation of melanins: Application to identification of dopamine-melanin</article-title><source>Pigment Cell Res.</source><year>1998</year><volume>11</volume><fpage>120</fpage><lpage>126</lpage><pub-id pub-id-type="doi">10.1111/j.1600-0749.1998.tb00721.x</pub-id><pub-id pub-id-type="pmid">9585251</pub-id></element-citation></ref><ref id="B121-biomolecules-05-01122"><label>121.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Halliday</surname><given-names>G.M.</given-names></name><name><surname>Ophof</surname><given-names>A.</given-names></name><name><surname>Broe</surname><given-names>M.</given-names></name><name><surname>Jensen</surname><given-names>P.H.</given-names></name><name><surname>Kettle</surname><given-names>E.</given-names></name><name><surname>Fedorow</surname><given-names>H.</given-names></name><name><surname>Cartwright</surname><given-names>M.I.</given-names></name><name><surname>Griffiths</surname><given-names>F.M.</given-names></name><name><surname>Shepherd</surname><given-names>C.E.</given-names></name><name><surname>Double</surname><given-names>K.L.</given-names></name></person-group><article-title>Alpha-synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson’s disease</article-title><source>Brain</source><year>2005</year><volume>128</volume><fpage>2654</fpage><lpage>2664</lpage><pub-id pub-id-type="doi">10.1093/brain/awh584</pub-id><pub-id pub-id-type="pmid">16000336</pub-id></element-citation></ref><ref id="B122-biomolecules-05-01122"><label>122.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>W.</given-names></name><name><surname>Yan</surname><given-names>Z.F.</given-names></name><name><surname>Gao</surname><given-names>J.H.</given-names></name><name><surname>Sun</surname><given-names>L.</given-names></name><name><surname>Huang</surname><given-names>X.Y.</given-names></name><name><surname>Liu</surname><given-names>Z.</given-names></name><name><surname>Yu</surname><given-names>S.Y.</given-names></name><name><surname>Cao</surname><given-names>C.J.</given-names></name><name><surname>Zuo</surname><given-names>L.J.</given-names></name><name><surname>Chen</surname><given-names>Z.J.</given-names></name><etal></etal></person-group><article-title>Role and mechanism of microglial activation in iron-induced selective and progressive dopaminergic neurodegeneration</article-title><source>Mol. Neurobiol.</source><year>2014</year><volume>49</volume><fpage>1153</fpage><lpage>1165</lpage><pub-id pub-id-type="doi">10.1007/s12035-013-8586-4</pub-id><pub-id pub-id-type="pmid">24277523</pub-id></element-citation></ref><ref id="B123-biomolecules-05-01122"><label>123.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilms</surname><given-names>H.</given-names></name><name><surname>Rosenstiel</surname><given-names>P.</given-names></name><name><surname>Sievers</surname><given-names>J.</given-names></name><name><surname>Deuschl</surname><given-names>G.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Lucius</surname><given-names>R.</given-names></name></person-group><article-title>Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: Implications for Parkinson’s disease</article-title><source>FASEB J.</source><year>2003</year><volume>17</volume><fpage>500</fpage><lpage>502</lpage><pub-id pub-id-type="pmid">12631585</pub-id></element-citation></ref><ref id="B124-biomolecules-05-01122"><label>124.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Basso</surname><given-names>E.</given-names></name><name><surname>Cupaioli</surname><given-names>F.A.</given-names></name><name><surname>Ferrari</surname><given-names>E.</given-names></name><name><surname>Sulzer</surname><given-names>D.</given-names></name><name><surname>Casella</surname><given-names>L.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name></person-group><article-title>Neuromelanin of the human substantia nigra: An update</article-title><source>Neurotox. Res.</source><year>2014</year><volume>25</volume><fpage>13</fpage><lpage>23</lpage><pub-id pub-id-type="doi">10.1007/s12640-013-9435-y</pub-id><pub-id pub-id-type="pmid">24155156</pub-id></element-citation></ref><ref id="B125-biomolecules-05-01122"><label>125.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ostergren</surname><given-names>A.</given-names></name><name><surname>Annas</surname><given-names>A.</given-names></name><name><surname>Skog</surname><given-names>K.</given-names></name><name><surname>Lindquist</surname><given-names>N.G.</given-names></name><name><surname>Brittebo</surname><given-names>E.B.</given-names></name></person-group><article-title>Longterm retention of neurotoxic beta-carbolines in brain neuromelanin</article-title><source>J. Neural Transm.</source><year>2004</year><volume>111</volume><fpage>141</fpage><lpage>157</lpage><pub-id pub-id-type="doi">10.1007/s00702-003-0080-0</pub-id><pub-id pub-id-type="pmid">14767717</pub-id></element-citation></ref><ref id="B126-biomolecules-05-01122"><label>126.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lindquist</surname><given-names>N.G.</given-names></name><name><surname>Larsson</surname><given-names>B.S.</given-names></name><name><surname>Lyden-Sokolowski</surname><given-names>A.</given-names></name></person-group><article-title>Autoradiography of [14C]paraquat or [14C]diquat in frogs and mice: Accumulation in neuromelanin</article-title><source>Neurosci. Lett.</source><year>1988</year><volume>93</volume><fpage>1</fpage><lpage>6</lpage><pub-id pub-id-type="doi">10.1016/0304-3940(88)90002-X</pub-id><pub-id pub-id-type="pmid">3264893</pub-id></element-citation></ref><ref id="B127-biomolecules-05-01122"><label>127.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Giaveri</surname><given-names>G.</given-names></name><name><surname>Gallorini</surname><given-names>M.</given-names></name><name><surname>Albertini</surname><given-names>A.</given-names></name><name><surname>Toscani</surname><given-names>M.</given-names></name><name><surname>Pezzoli</surname><given-names>G.</given-names></name><name><surname>Lucius</surname><given-names>R.</given-names></name><name><surname>Wilms</surname><given-names>H.</given-names></name><name><surname>Sulzer</surname><given-names>D.</given-names></name><name><surname>Ito</surname><given-names>S.</given-names></name><etal></etal></person-group><article-title>The neuromelanin of human substantia nigra: Physiological and pathogenic aspects</article-title><source>Pigment Cell Res.</source><year>2004</year><volume>17</volume><fpage>610</fpage><lpage>617</lpage><pub-id pub-id-type="doi">10.1111/j.1600-0749.2004.00201.x</pub-id><pub-id pub-id-type="pmid">15541018</pub-id></element-citation></ref><ref id="B128-biomolecules-05-01122"><label>128.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Mecacci</surname><given-names>C.</given-names></name><name><surname>Seraglia</surname><given-names>R.</given-names></name><name><surname>Parati</surname><given-names>E.</given-names></name></person-group><article-title>The chemical characterization of melanin contained in substantia nigra of human brain</article-title><source>Biochim. Biophys. Acta</source><year>1992</year><volume>1138</volume><fpage>6</fpage><lpage>10</lpage><pub-id pub-id-type="doi">10.1016/0925-4439(92)90144-C</pub-id><pub-id pub-id-type="pmid">1737070</pub-id></element-citation></ref><ref id="B129-biomolecules-05-01122"><label>129.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Costi</surname><given-names>P.</given-names></name><name><surname>Mecacci</surname><given-names>C.</given-names></name><name><surname>Ito</surname><given-names>S.</given-names></name><name><surname>Terreni</surname><given-names>M.</given-names></name><name><surname>Sonnino</surname><given-names>S.</given-names></name></person-group><article-title>Interaction of human substantia nigra neuromelanin with lipids and peptides</article-title><source>J. Neurochem.</source><year>2000</year><volume>74</volume><fpage>1758</fpage><lpage>1765</lpage><pub-id pub-id-type="doi">10.1046/j.1471-4159.2000.0741758.x</pub-id><pub-id pub-id-type="pmid">10737635</pub-id></element-citation></ref><ref id="B130-biomolecules-05-01122"><label>130.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aime</surname><given-names>S.</given-names></name><name><surname>Fasano</surname><given-names>M.</given-names></name><name><surname>Bergamasco</surname><given-names>B.</given-names></name><name><surname>Lopiano</surname><given-names>L.</given-names></name><name><surname>Valente</surname><given-names>G.</given-names></name></person-group><article-title>Evidence for a glycidic-lipidic matrix in human neuromelanin, potentially responsible for the enhanced iron sequestering ability of substantia nigra</article-title><source>J. Neurochem.</source><year>1994</year><volume>62</volume><fpage>369</fpage><lpage>371</lpage><pub-id pub-id-type="doi">10.1046/j.1471-4159.1994.62010369.x</pub-id><pub-id pub-id-type="pmid">8263538</pub-id></element-citation></ref><ref id="B131-biomolecules-05-01122"><label>131.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barden</surname><given-names>H.</given-names></name></person-group><article-title>The histochemical relationship of neuromelanin and lipofuscin</article-title><source>J. Neuropathol. Exp. Neurol.</source><year>1969</year><volume>28</volume><fpage>419</fpage><lpage>441</lpage><pub-id pub-id-type="doi">10.1097/00005072-196907000-00005</pub-id><pub-id pub-id-type="pmid">4978022</pub-id></element-citation></ref><ref id="B132-biomolecules-05-01122"><label>132.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Swartz</surname><given-names>H.M.</given-names></name><name><surname>Sarna</surname><given-names>T.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name></person-group><article-title>Modulation by neuromelanin of the availability and reactivity of metal ions</article-title><source>Ann. Neurol.</source><year>1992</year><volume>32</volume><fpage>S69</fpage><lpage>S75</lpage><pub-id pub-id-type="doi">10.1002/ana.410320712</pub-id><pub-id pub-id-type="pmid">1510383</pub-id></element-citation></ref><ref id="B133-biomolecules-05-01122"><label>133.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Bellei</surname><given-names>C.</given-names></name><name><surname>Giannelli</surname><given-names>S.</given-names></name><name><surname>Terreni</surname><given-names>M.R.</given-names></name><name><surname>Gallorini</surname><given-names>M.</given-names></name><name><surname>Rizzio</surname><given-names>E.</given-names></name><name><surname>Pezzoli</surname><given-names>G.</given-names></name><name><surname>Albertini</surname><given-names>A.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name></person-group><article-title>Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: Consequences for neuronal vulnerability</article-title><source>J. Neural. Transm.</source><year>2006</year><volume>113</volume><fpage>757</fpage><lpage>767</lpage><pub-id pub-id-type="doi">10.1007/s00702-006-0453-2</pub-id><pub-id pub-id-type="pmid">16755380</pub-id></element-citation></ref><ref id="B134-biomolecules-05-01122"><label>134.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Faucheux</surname><given-names>B.A.</given-names></name><name><surname>Martin</surname><given-names>M.E.</given-names></name><name><surname>Beaumont</surname><given-names>C.</given-names></name><name><surname>Hauw</surname><given-names>J.J.</given-names></name><name><surname>Agid</surname><given-names>Y.</given-names></name><name><surname>Hirsch</surname><given-names>E.C.</given-names></name></person-group><article-title>Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson’s disease</article-title><source>J. Neurochem.</source><year>2003</year><volume>86</volume><fpage>1142</fpage><lpage>1148</lpage><pub-id pub-id-type="doi">10.1046/j.1471-4159.2003.01923.x</pub-id><pub-id pub-id-type="pmid">12911622</pub-id></element-citation></ref><ref id="B135-biomolecules-05-01122"><label>135.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Double</surname><given-names>K.L.</given-names></name><name><surname>Gerlach</surname><given-names>M.</given-names></name><name><surname>Schunemann</surname><given-names>V.</given-names></name><name><surname>Trautwein</surname><given-names>A.X.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Gallorini</surname><given-names>M.</given-names></name><name><surname>Youdim</surname><given-names>M.B.</given-names></name><name><surname>Riederer</surname><given-names>P.</given-names></name><name><surname>Ben-Shachar</surname><given-names>D.</given-names></name></person-group><article-title>Iron-binding characteristics of neuromelanin of the human substantia nigra</article-title><source>Biochem. Pharmacol.</source><year>2003</year><volume>66</volume><fpage>489</fpage><lpage>494</lpage><pub-id pub-id-type="doi">10.1016/S0006-2952(03)00293-4</pub-id><pub-id pub-id-type="pmid">12907248</pub-id></element-citation></ref><ref id="B136-biomolecules-05-01122"><label>136.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ben-Shachar</surname><given-names>D.</given-names></name><name><surname>Riederer</surname><given-names>P.</given-names></name><name><surname>Youdim</surname><given-names>M.B.</given-names></name></person-group><article-title>Iron-melanin interaction and lipid peroxidation: Implications for Parkinson’s disease</article-title><source>J. Neurochem.</source><year>1991</year><volume>57</volume><fpage>1609</fpage><lpage>1614</lpage><pub-id pub-id-type="doi">10.1111/j.1471-4159.1991.tb06358.x</pub-id><pub-id pub-id-type="pmid">1919577</pub-id></element-citation></ref><ref id="B137-biomolecules-05-01122"><label>137.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gründemann</surname><given-names>J.</given-names></name><name><surname>Schlaudraff</surname><given-names>F.</given-names></name><name><surname>Liss</surname><given-names>B.</given-names></name></person-group><article-title>UV-laser microdissection and mRNA expression analysis of individual neurons from postmortem Parkinson’s disease brains</article-title><source>Methods Mol. Biol.</source><year>2011</year><volume>755</volume><fpage>363</fpage><lpage>374</lpage><pub-id pub-id-type="pmid">21761319</pub-id></element-citation></ref><ref id="B138-biomolecules-05-01122"><label>138.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsuo</surname><given-names>Y.</given-names></name><name><surname>Kamitani</surname><given-names>T.</given-names></name></person-group><article-title>Parkinson’s disease-related protein, α-synuclein, in malignant melanoma</article-title><source>PLoS ONE</source><year>2010</year><volume>5</volume><fpage>e10481</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0010481</pub-id><pub-id pub-id-type="pmid">20463956</pub-id></element-citation></ref><ref id="B139-biomolecules-05-01122"><label>139.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fasano</surname><given-names>M.</given-names></name><name><surname>Giraudo</surname><given-names>S.</given-names></name><name><surname>Coha</surname><given-names>S.</given-names></name><name><surname>Bergamasco</surname><given-names>B.</given-names></name><name><surname>Lopiano</surname><given-names>L.</given-names></name></person-group><article-title>Residual substantia nigra neuromelanin in Parkinson’s disease is cross-linked to alpha-synuclein</article-title><source>Neurochem. Int.</source><year>2003</year><volume>42</volume><fpage>603</fpage><lpage>606</lpage><pub-id pub-id-type="doi">10.1016/S0197-0186(02)00161-4</pub-id><pub-id pub-id-type="pmid">12590943</pub-id></element-citation></ref><ref id="B140-biomolecules-05-01122"><label>140.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fedorow</surname><given-names>H.</given-names></name><name><surname>Halliday</surname><given-names>G.M.</given-names></name><name><surname>Rickert</surname><given-names>C.H.</given-names></name><name><surname>Gerlach</surname><given-names>M.</given-names></name><name><surname>Riederer</surname><given-names>P.</given-names></name><name><surname>Double</surname><given-names>K.L.</given-names></name></person-group><article-title>Evidence for specific phases in the development of human neuromelanin</article-title><source>Neurobiol. Aging</source><year>2006</year><volume>27</volume><fpage>506</fpage><lpage>512</lpage><pub-id pub-id-type="doi">10.1016/j.neurobiolaging.2005.02.015</pub-id><pub-id pub-id-type="pmid">15916835</pub-id></element-citation></ref><ref id="B141-biomolecules-05-01122"><label>141.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chu</surname><given-names>Y.</given-names></name><name><surname>Kordower</surname><given-names>J.H.</given-names></name></person-group><article-title>Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson’s disease?</article-title><source>Neurobiol. Dis.</source><year>2007</year><volume>25</volume><fpage>134</fpage><lpage>149</lpage><pub-id pub-id-type="doi">10.1016/j.nbd.2006.08.021</pub-id><pub-id pub-id-type="pmid">17055279</pub-id></element-citation></ref><ref id="B142-biomolecules-05-01122"><label>142.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Double</surname><given-names>K.L.</given-names></name><name><surname>Ben-Shachar</surname><given-names>D.</given-names></name><name><surname>Youdim</surname><given-names>M.B.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Riederer</surname><given-names>P.</given-names></name><name><surname>Gerlach</surname><given-names>M.</given-names></name></person-group><article-title>Influence of neuromelanin on oxidative pathways within the human substantia nigra</article-title><source>Neurotoxicol. Teratol.</source><year>2002</year><volume>24</volume><fpage>621</fpage><lpage>628</lpage><pub-id pub-id-type="doi">10.1016/S0892-0362(02)00218-0</pub-id><pub-id pub-id-type="pmid">12200193</pub-id></element-citation></ref><ref id="B143-biomolecules-05-01122"><label>143.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shamoto-Nagai</surname><given-names>M.</given-names></name><name><surname>Maruyama</surname><given-names>W.</given-names></name><name><surname>Yi</surname><given-names>H.</given-names></name><name><surname>Akao</surname><given-names>Y.</given-names></name><name><surname>Tribl</surname><given-names>F.</given-names></name><name><surname>Gerlach</surname><given-names>M.</given-names></name><name><surname>Osawa</surname><given-names>T.</given-names></name><name><surname>Riederer</surname><given-names>P.</given-names></name><name><surname>Naoi</surname><given-names>M.</given-names></name></person-group><article-title>Neuromelanin induces oxidative stress in mitochondria through release of iron: Mechanism behind the inhibition of 26S proteasome</article-title><source>J. Neural Transm.</source><year>2006</year><volume>113</volume><fpage>633</fpage><lpage>644</lpage><pub-id pub-id-type="doi">10.1007/s00702-005-0410-5</pub-id><pub-id pub-id-type="pmid">16362626</pub-id></element-citation></ref><ref id="B144-biomolecules-05-01122"><label>144.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sulzer</surname><given-names>D.</given-names></name></person-group><article-title>Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease</article-title><source>Trends Neurosci.</source><year>2007</year><volume>30</volume><fpage>244</fpage><lpage>250</lpage><pub-id pub-id-type="doi">10.1016/j.tins.2007.03.009</pub-id><pub-id pub-id-type="pmid">17418429</pub-id></element-citation></ref><ref id="B145-biomolecules-05-01122"><label>145.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Webb</surname><given-names>J.L.</given-names></name><name><surname>Ravikumar</surname><given-names>B.</given-names></name><name><surname>Atkins</surname><given-names>J.</given-names></name><name><surname>Skepper</surname><given-names>J.N.</given-names></name><name><surname>Rubinsztein</surname><given-names>D.C.</given-names></name></person-group><article-title>Alpha-Synuclein is degraded by both autophagy and the proteasome</article-title><source>J. Biol. Chem.</source><year>2003</year><volume>278</volume><fpage>25009</fpage><lpage>25013</lpage><pub-id pub-id-type="doi">10.1074/jbc.M300227200</pub-id><pub-id pub-id-type="pmid">12719433</pub-id></element-citation></ref><ref id="B146-biomolecules-05-01122"><label>146.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pan</surname><given-names>T.</given-names></name><name><surname>Zhu</surname><given-names>J.</given-names></name><name><surname>Hwu</surname><given-names>W.J.</given-names></name><name><surname>Jankovic</surname><given-names>J.</given-names></name></person-group><article-title>The role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells</article-title><source>PLoS ONE</source><year>2012</year><volume>7</volume><fpage>e45183</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0045183</pub-id><pub-id pub-id-type="pmid">23028833</pub-id></element-citation></ref><ref id="B147-biomolecules-05-01122"><label>147.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Costi</surname><given-names>P.</given-names></name><name><surname>Tampellini</surname><given-names>D.</given-names></name><name><surname>Gatti</surname><given-names>A.</given-names></name><name><surname>Gerlach</surname><given-names>M.</given-names></name><name><surname>Riederer</surname><given-names>P.</given-names></name><name><surname>Fariello</surname><given-names>R.G.</given-names></name><name><surname>Ito</surname><given-names>S.</given-names></name><name><surname>Gallorini</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>The neuromelanin of human substantia nigra: Structure, synthesis and molecular behaviour</article-title><source>J. Neural Transm. Suppl.</source><year>2003</year><volume>65</volume><fpage>145</fpage><lpage>155</lpage><pub-id pub-id-type="pmid">12946053</pub-id></element-citation></ref><ref id="B148-biomolecules-05-01122"><label>148.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wakamatsu</surname><given-names>K.</given-names></name><name><surname>Murase</surname><given-names>T.</given-names></name><name><surname>Zucca</surname><given-names>F.A.</given-names></name><name><surname>Zecca</surname><given-names>L.</given-names></name><name><surname>Ito</surname><given-names>S.</given-names></name></person-group><article-title>Biosynthetic pathway to neuromelanin and its aging process</article-title><source>Pigment Cell Melanoma Res.</source><year>2012</year><volume>25</volume><fpage>792</fpage><lpage>803</lpage><pub-id pub-id-type="doi">10.1111/pcmr.12014</pub-id><pub-id pub-id-type="pmid">22938712</pub-id></element-citation></ref><ref id="B149-biomolecules-05-01122"><label>149.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tessari</surname><given-names>I.</given-names></name><name><surname>Bisaglia</surname><given-names>M.</given-names></name><name><surname>Valle</surname><given-names>F.</given-names></name><name><surname>Samorì</surname><given-names>B.</given-names></name><name><surname>Bergantino</surname><given-names>E.</given-names></name><name><surname>Mammi</surname><given-names>S.</given-names></name><name><surname>Bubacco</surname><given-names>L.</given-names></name></person-group><article-title>The reaction of alpha-synuclein with tyrosinase: Possible implications for Parkinson disease</article-title><source>J. Biol. Chem.</source><year>2008</year><volume>283</volume><fpage>16808</fpage><lpage>16817</lpage><pub-id pub-id-type="doi">10.1074/jbc.M709014200</pub-id><pub-id pub-id-type="pmid">18390556</pub-id></element-citation></ref><ref id="B150-biomolecules-05-01122"><label>150.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>Y.H.</given-names></name><name><surname>Gao</surname><given-names>N.</given-names></name><name><surname>Ye</surname><given-names>Y.W.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name><name><surname>Yu</surname><given-names>S.</given-names></name><name><surname>Yang</surname><given-names>H.</given-names></name><name><surname>Uéda</surname><given-names>K.</given-names></name><name><surname>Chan</surname><given-names>P.</given-names></name></person-group><article-title>α-Synuclein functions as a negative regulator for expression of tyrosine hudroxylase</article-title><source>Acta Neurol. Belg.</source><year>2011</year><volume>111</volume><fpage>130</fpage><lpage>135</lpage><pub-id pub-id-type="pmid">21748932</pub-id></element-citation></ref><ref id="B151-biomolecules-05-01122"><label>151.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Koo</surname><given-names>H.J.</given-names></name><name><surname>Yang</surname><given-names>J.E.</given-names></name><name><surname>Park</surname><given-names>J.H.</given-names></name><name><surname>Lee</surname><given-names>D.</given-names></name><name><surname>Paik</surname><given-names>S.R.</given-names></name></person-group><article-title>α-Synuclein-mediated defense against oxidative stress via modulation of glutathione peroxidase</article-title><source>Biochim. Biophys. Acta</source><year>2013</year><volume>1834</volume><fpage>972</fpage><lpage>976</lpage><pub-id pub-id-type="doi">10.1016/j.bbapap.2013.03.008</pub-id><pub-id pub-id-type="pmid">23507046</pub-id></element-citation></ref><ref id="B152-biomolecules-05-01122"><label>152.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fornstedt</surname><given-names>B.</given-names></name><name><surname>Rosengren</surname><given-names>E.</given-names></name><name><surname>Carlsson</surname><given-names>A.</given-names></name></person-group><article-title>Occurrence and distribution of 5-S-cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian species</article-title><source>Neuropharmacology</source><year>1986</year><volume>25</volume><fpage>451</fpage><lpage>454</lpage><pub-id pub-id-type="doi">10.1016/0028-3908(86)90242-X</pub-id><pub-id pub-id-type="pmid">3086766</pub-id></element-citation></ref><ref id="B153-biomolecules-05-01122"><label>153.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liang</surname><given-names>C.L.</given-names></name><name><surname>Nelson</surname><given-names>O.</given-names></name><name><surname>Yazdani</surname><given-names>U.</given-names></name><name><surname>Pasbakhsh</surname><given-names>P.</given-names></name><name><surname>German</surname><given-names>D.C.</given-names></name></person-group><article-title>Inverse relationship between the contents of neuromelanin pigment and the vesicular monoamine transporter-2: Human midbrain dopamine neurons</article-title><source>J. Comp. Neurol.</source><year>2004</year><volume>473</volume><fpage>97</fpage><lpage>106</lpage><pub-id pub-id-type="doi">10.1002/cne.20098</pub-id><pub-id pub-id-type="pmid">15067721</pub-id></element-citation></ref><ref id="B154-biomolecules-05-01122"><label>154.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yu</surname><given-names>S.</given-names></name><name><surname>Zuo</surname><given-names>X.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Zhang</surname><given-names>C.</given-names></name><name><surname>Zhou</surname><given-names>M.</given-names></name><name><surname>Zhang</surname><given-names>Y.A.</given-names></name><name><surname>Uéda</surname><given-names>K.</given-names></name><name><surname>Chan</surname><given-names>P.</given-names></name></person-group><article-title>Inhibition of tyrosine hydroxylase expression in alpha-synuclein-transfected dopaminergic neuronal cells</article-title><source>Neurosci. Lett.</source><year>2004</year><volume>367</volume><fpage>34</fpage><lpage>39</lpage><pub-id pub-id-type="doi">10.1016/j.neulet.2004.05.118</pub-id><pub-id pub-id-type="pmid">15308292</pub-id></element-citation></ref><ref id="B155-biomolecules-05-01122"><label>155.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abeliovich</surname><given-names>A.</given-names></name><name><surname>Schmitz</surname><given-names>Y.</given-names></name><name><surname>Fariñas</surname><given-names>I.</given-names></name><name><surname>Choi-Lundberg</surname><given-names>D.</given-names></name><name><surname>Ho</surname><given-names>W.H.</given-names></name><name><surname>Castillo</surname><given-names>P.E.</given-names></name><name><surname>Shinsky</surname><given-names>N.</given-names></name><name><surname>Verdugo</surname><given-names>J.M.</given-names></name><name><surname>Armanini</surname><given-names>M.</given-names></name><name><surname>Ryan</surname><given-names>A.</given-names></name><etal></etal></person-group><article-title>Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system</article-title><source>Neuron</source><year>2000</year><volume>25</volume><fpage>239</fpage><lpage>252</lpage><pub-id pub-id-type="doi">10.1016/S0896-6273(00)80886-7</pub-id><pub-id pub-id-type="pmid">10707987</pub-id></element-citation></ref><ref id="B156-biomolecules-05-01122"><label>156.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Larsen</surname><given-names>K.E.</given-names></name><name><surname>Schmitz</surname><given-names>Y.</given-names></name><name><surname>Troyer</surname><given-names>M.D.</given-names></name><name><surname>Mosharov</surname><given-names>E.</given-names></name><name><surname>Dietrich</surname><given-names>P.</given-names></name><name><surname>Quazi</surname><given-names>A.Z.</given-names></name><name><surname>Savalle</surname><given-names>M.</given-names></name><name><surname>Nemani</surname><given-names>V.</given-names></name><name><surname>Chaudhry</surname><given-names>F.A.</given-names></name><name><surname>Edwards</surname><given-names>R.H.</given-names></name><etal></etal></person-group><article-title>Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis</article-title><source>J. Neurosci.</source><year>2006</year><volume>26</volume><fpage>11915</fpage><lpage>11922</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.3821-06.2006</pub-id><pub-id pub-id-type="pmid">17108165</pub-id></element-citation></ref><ref id="B157-biomolecules-05-01122"><label>157.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bellucci</surname><given-names>A.</given-names></name><name><surname>Navarria</surname><given-names>L.</given-names></name><name><surname>Falarti</surname><given-names>E.</given-names></name><name><surname>Zaltieri</surname><given-names>M.</given-names></name><name><surname>Bono</surname><given-names>F.</given-names></name><name><surname>Collo</surname><given-names>G.</given-names></name><name><surname>Spillantini</surname><given-names>M.G.</given-names></name><name><surname>Missale</surname><given-names>C.</given-names></name><name><surname>Spano</surname><given-names>P.</given-names></name></person-group><article-title>Redistribution of DAT/α-synuclein complexes visualized by “<italic>in situ</italic>” proximity ligation assay in transgenic mice modelling early Parkinson’s disease</article-title><source>PLoS ONE</source><year>2011</year><volume>6</volume><fpage>e27959</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0027959</pub-id><pub-id pub-id-type="pmid">22163275</pub-id></element-citation></ref><ref id="B158-biomolecules-05-01122"><label>158.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oaks</surname><given-names>A.W.</given-names></name><name><surname>Marsh-Armstrong</surname><given-names>N.</given-names></name><name><surname>Jones</surname><given-names>J.M.</given-names></name><name><surname>Credle</surname><given-names>J.J.</given-names></name><name><surname>Sidhu</surname><given-names>A.</given-names></name></person-group><article-title>Synucleins antagonize endoplasmic reticulum function to modulate dopamine transporter trafficking</article-title><source>PLoS ONE</source><year>2013</year><volume>8</volume><fpage>e70872</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0070872</pub-id><pub-id pub-id-type="pmid">23967127</pub-id></element-citation></ref><ref id="B159-biomolecules-05-01122"><label>159.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lotharius</surname><given-names>J.</given-names></name><name><surname>Brundin</surname><given-names>P.</given-names></name></person-group><article-title>Pathogenesis of Parkinson’s disease: Dopamine, vesicles and α-synuclein</article-title><source>Nat. Rev. Neurosci.</source><year>2002</year><volume>3</volume><fpage>932</fpage><lpage>942</lpage><pub-id pub-id-type="doi">10.1038/nrn983</pub-id><pub-id pub-id-type="pmid">12461550</pub-id></element-citation></ref><ref id="B160-biomolecules-05-01122"><label>160.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lotharius</surname><given-names>J.</given-names></name><name><surname>Barg</surname><given-names>S.</given-names></name><name><surname>Wiekop</surname><given-names>P.</given-names></name><name><surname>Lundberg</surname><given-names>C.</given-names></name><name><surname>Raymon</surname><given-names>H.K.</given-names></name><name><surname>Brundin</surname><given-names>P.</given-names></name></person-group><article-title>Effect of mutant α-synuclein on dopamine homeostasis in a new human mesencephalic cell line</article-title><source>J. Biol. Chem.</source><year>2002</year><volume>277</volume><fpage>38884</fpage><lpage>38894</lpage><pub-id pub-id-type="doi">10.1074/jbc.M205518200</pub-id><pub-id pub-id-type="pmid">12145295</pub-id></element-citation></ref><ref id="B161-biomolecules-05-01122"><label>161.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mosharov</surname><given-names>E.V.</given-names></name><name><surname>Staal</surname><given-names>R.G.</given-names></name><name><surname>Bove</surname><given-names>J.</given-names></name><name><surname>Prou</surname><given-names>D.</given-names></name><name><surname>Hananiya</surname><given-names>A.</given-names></name><name><surname>Markov</surname><given-names>D.</given-names></name><name><surname>Poulsen</surname><given-names>N.</given-names></name><name><surname>Larsen</surname><given-names>K.E.</given-names></name><name><surname>Moore</surname><given-names>C.M.</given-names></name><name><surname>Troyer</surname><given-names>M.D.</given-names></name><etal></etal></person-group><article-title>Alpha-synuclein overexpression increases cytosolic catecholamine concentration</article-title><source>J. Neurosci.</source><year>2006</year><volume>26</volume><fpage>9304</fpage><lpage>9311</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.0519-06.2006</pub-id><pub-id pub-id-type="pmid">16957086</pub-id></element-citation></ref><ref id="B162-biomolecules-05-01122"><label>162.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>T.</given-names></name><name><surname>Chow</surname><given-names>A.M.</given-names></name><name><surname>Cheng</surname><given-names>X.R.</given-names></name><name><surname>Tang</surname><given-names>D.W.</given-names></name><name><surname>Brown</surname><given-names>I.R.</given-names></name><name><surname>Kerman</surname><given-names>K.</given-names></name></person-group><article-title>Oxidative stress effect of dopamine on α-synuclein: Electroanalysis of solvent interactions</article-title><source>ACS Chem. Neurosci.</source><year>2012</year><volume>3</volume><fpage>569</fpage><lpage>574</lpage><pub-id pub-id-type="doi">10.1021/cn300034t</pub-id><pub-id pub-id-type="pmid">22860226</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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