Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species.
Identifieur interne : 000007 ( PubMed/Checkpoint ); précédent : 000006; suivant : 000008Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species.
Auteurs : Florencia González-Lizárraga [Argentine] ; Sergio B. Socías [Argentine] ; César L. Ávila [Argentine] ; Clarisa M. Torres-Bugeau [Argentine] ; Leandro R S. Barbosa [Brésil] ; Andres Binolfi [Argentine] ; Julia E. Sepúlveda-Díaz [France] ; Elaine Del-Bel [Brésil] ; Claudio O. Fernandez [Argentine] ; Dulce Papy-Garcia [France] ; Rosangela Itri [Brésil] ; Rita Raisman-Vozari [France] ; Rosana N. Chehín [Argentine]Source :
- Scientific reports [ 2045-2322 ] ; 2017.
Abstract
Synucleinophaties are progressive neurodegenerative disorders with no cure to date. An attractive strategy to tackle this problem is repurposing already tested safe drugs against novel targets. In this way, doxycycline prevents neurodegeneration in Parkinson models by modulating neuroinflammation. However, anti-inflammatory therapy per se is insufficient to account for neuroprotection. Herein we characterise novel targets of doxycycline describing the structural background supporting its effectiveness as a neuroprotector at subantibiotic doses. Our results show that doxycycline reshapes α-synuclein oligomers into off-pathway, high-molecular-weight species that do not evolve into fibrils. Off-pathway species present less hydrophobic surface than on-pathway oligomers and display different β-sheet structural arrangement. These structural changes affect the α-synuclein ability to destabilize biological membranes, cell viability, and formation of additional toxic species. Altogether, these mechanisms could act synergically giving novel targets for repurposing this drug.
DOI: 10.1038/srep41755
PubMed: 28155912
Affiliations:
- Argentine, Brésil, France
- État de São Paulo, Île-de-France
- Créteil, Paris, São Paulo
- Université de São Paulo
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Chehín</name><affiliation wicri:level="1"><nlm:affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán</wicri:regionArea><wicri:noRegion>Chacabuco 461 (T4000ILI) Tucumán</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28155912</idno><idno type="pmid">28155912</idno><idno type="doi">10.1038/srep41755</idno><idno type="wicri:Area/PubMed/Corpus">000008</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000008</idno><idno type="wicri:Area/PubMed/Curation">000008</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000008</idno><idno type="wicri:Area/PubMed/Checkpoint">000008</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000008</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species.</title><author><name sortKey="Gonzalez Lizarraga, Florencia" sort="Gonzalez Lizarraga, Florencia" uniqKey="Gonzalez Lizarraga F" first="Florencia" last="González-Lizárraga">Florencia González-Lizárraga</name><affiliation wicri:level="1"><nlm:affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán</wicri:regionArea><wicri:noRegion>Chacabuco 461 (T4000ILI) Tucumán</wicri:noRegion></affiliation></author><author><name sortKey="Socias, Sergio B" sort="Socias, Sergio B" uniqKey="Socias S" first="Sergio B" last="Socías">Sergio B. Socías</name><affiliation wicri:level="1"><nlm:affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán</wicri:regionArea><wicri:noRegion>Chacabuco 461 (T4000ILI) Tucumán</wicri:noRegion></affiliation></author><author><name sortKey="Avila, Cesar L" sort="Avila, Cesar L" uniqKey="Avila C" first="César L" last="Ávila">César L. Ávila</name><affiliation wicri:level="1"><nlm:affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán</wicri:regionArea><wicri:noRegion>Chacabuco 461 (T4000ILI) Tucumán</wicri:noRegion></affiliation></author><author><name sortKey="Torres Bugeau, Clarisa M" sort="Torres Bugeau, Clarisa M" uniqKey="Torres Bugeau C" first="Clarisa M" last="Torres-Bugeau">Clarisa M. Torres-Bugeau</name><affiliation wicri:level="1"><nlm:affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán</wicri:regionArea><wicri:noRegion>Chacabuco 461 (T4000ILI) Tucumán</wicri:noRegion></affiliation></author><author><name sortKey="Barbosa, Leandro R S" sort="Barbosa, Leandro R S" uniqKey="Barbosa L" first="Leandro R S" last="Barbosa">Leandro R S. Barbosa</name><affiliation wicri:level="3"><nlm:affiliation>Instituto de Física da Universidade de São Paulo - IFUSP, Rua do Matão, Travessa R, 187, São Paulo, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto de Física da Universidade de São Paulo - IFUSP, Rua do Matão, Travessa R, 187, São Paulo</wicri:regionArea><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Binolfi, Andres" sort="Binolfi, Andres" uniqKey="Binolfi A" first="Andres" last="Binolfi">Andres Binolfi</name><affiliation wicri:level="1"><nlm:affiliation>Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario</wicri:regionArea><wicri:noRegion>S2002LRK Rosario</wicri:noRegion></affiliation></author><author><name sortKey="Sepulveda Diaz, Julia E" sort="Sepulveda Diaz, Julia E" uniqKey="Sepulveda Diaz J" first="Julia E" last="Sepúlveda-Díaz">Julia E. Sepúlveda-Díaz</name><affiliation wicri:level="3"><nlm:affiliation>Institut National De La Santé Et De La Recherche Médicale, U 1127, CNRS, Unité Mixte De Recherche (UMR) 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau Et De La Moelle Epinière, ICM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National De La Santé Et De La Recherche Médicale, U 1127, CNRS, Unité Mixte De Recherche (UMR) 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau Et De La Moelle Epinière, ICM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Del Bel, Elaine" sort="Del Bel, Elaine" uniqKey="Del Bel E" first="Elaine" last="Del-Bel">Elaine Del-Bel</name><affiliation wicri:level="4"><nlm:affiliation>Department of Morphology, Physiology and Stomatology, Faculty of Odontology of Ribeirão Preto, University of São Paulo, Brazil, Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Department of Morphology, Physiology and Stomatology, Faculty of Odontology of Ribeirão Preto, University of São Paulo, Brazil, Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo</wicri:regionArea><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName><orgName type="university">Université de São Paulo</orgName></affiliation></author><author><name sortKey="Fernandez, Claudio O" sort="Fernandez, Claudio O" uniqKey="Fernandez C" first="Claudio O" last="Fernandez">Claudio O. Fernandez</name><affiliation wicri:level="1"><nlm:affiliation>Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario</wicri:regionArea><wicri:noRegion>S2002LRK Rosario</wicri:noRegion></affiliation></author><author><name sortKey="Papy Garcia, Dulce" sort="Papy Garcia, Dulce" uniqKey="Papy Garcia D" first="Dulce" last="Papy-Garcia">Dulce Papy-Garcia</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire Croissance, Réparation et Régénération Tissulaires (CRRET), CNRS ERL 9215, Université Paris Est Créteil, Université Paris Est, F-94000, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Croissance, Réparation et Régénération Tissulaires (CRRET), CNRS ERL 9215, Université Paris Est Créteil, Université Paris Est, F-94000, Créteil</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Itri, Rosangela" sort="Itri, Rosangela" uniqKey="Itri R" first="Rosangela" last="Itri">Rosangela Itri</name><affiliation wicri:level="3"><nlm:affiliation>Instituto de Física da Universidade de São Paulo - IFUSP, Rua do Matão, Travessa R, 187, São Paulo, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto de Física da Universidade de São Paulo - IFUSP, Rua do Matão, Travessa R, 187, São Paulo</wicri:regionArea><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name><affiliation wicri:level="3"><nlm:affiliation>Institut National De La Santé Et De La Recherche Médicale, U 1127, CNRS, Unité Mixte De Recherche (UMR) 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau Et De La Moelle Epinière, ICM, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National De La Santé Et De La Recherche Médicale, U 1127, CNRS, Unité Mixte De Recherche (UMR) 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau Et De La Moelle Epinière, ICM, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Chehin, Rosana N" sort="Chehin, Rosana N" uniqKey="Chehin R" first="Rosana N" last="Chehín">Rosana N. Chehín</name><affiliation wicri:level="1"><nlm:affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán</wicri:regionArea><wicri:noRegion>Chacabuco 461 (T4000ILI) Tucumán</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Synucleinophaties are progressive neurodegenerative disorders with no cure to date. An attractive strategy to tackle this problem is repurposing already tested safe drugs against novel targets. In this way, doxycycline prevents neurodegeneration in Parkinson models by modulating neuroinflammation. However, anti-inflammatory therapy per se is insufficient to account for neuroprotection. Herein we characterise novel targets of doxycycline describing the structural background supporting its effectiveness as a neuroprotector at subantibiotic doses. Our results show that doxycycline reshapes α-synuclein oligomers into off-pathway, high-molecular-weight species that do not evolve into fibrils. Off-pathway species present less hydrophobic surface than on-pathway oligomers and display different β-sheet structural arrangement. These structural changes affect the α-synuclein ability to destabilize biological membranes, cell viability, and formation of additional toxic species. Altogether, these mechanisms could act synergically giving novel targets for repurposing this drug.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">28155912</PMID><DateCreated><Year>2017</Year><Month>02</Month><Day>03</Day></DateCreated><DateRevised><Year>2017</Year><Month>02</Month><Day>07</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>7</Volume><PubDate><Year>2017</Year><Month>Feb</Month><Day>03</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species.</ArticleTitle><Pagination><MedlinePgn>41755</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/srep41755</ELocationID><Abstract><AbstractText NlmCategory="UNASSIGNED">Synucleinophaties are progressive neurodegenerative disorders with no cure to date. An attractive strategy to tackle this problem is repurposing already tested safe drugs against novel targets. In this way, doxycycline prevents neurodegeneration in Parkinson models by modulating neuroinflammation. However, anti-inflammatory therapy per se is insufficient to account for neuroprotection. Herein we characterise novel targets of doxycycline describing the structural background supporting its effectiveness as a neuroprotector at subantibiotic doses. Our results show that doxycycline reshapes α-synuclein oligomers into off-pathway, high-molecular-weight species that do not evolve into fibrils. Off-pathway species present less hydrophobic surface than on-pathway oligomers and display different β-sheet structural arrangement. These structural changes affect the α-synuclein ability to destabilize biological membranes, cell viability, and formation of additional toxic species. Altogether, these mechanisms could act synergically giving novel targets for repurposing this drug.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>González-Lizárraga</LastName><ForeName>Florencia</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut National De La Santé Et De La Recherche Médicale, U 1127, CNRS, Unité Mixte De Recherche (UMR) 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau Et De La Moelle Epinière, ICM, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Socías</LastName><ForeName>Sergio B</ForeName><Initials>SB</Initials><AffiliationInfo><Affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ávila</LastName><ForeName>César L</ForeName><Initials>CL</Initials><AffiliationInfo><Affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Torres-Bugeau</LastName><ForeName>Clarisa M</ForeName><Initials>CM</Initials><AffiliationInfo><Affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barbosa</LastName><ForeName>Leandro R S</ForeName><Initials>LR</Initials><AffiliationInfo><Affiliation>Instituto de Física da Universidade de São Paulo - IFUSP, Rua do Matão, Travessa R, 187, São Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Binolfi</LastName><ForeName>Andres</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sepúlveda-Díaz</LastName><ForeName>Julia E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Institut National De La Santé Et De La Recherche Médicale, U 1127, CNRS, Unité Mixte De Recherche (UMR) 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau Et De La Moelle Epinière, ICM, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Del-Bel</LastName><ForeName>Elaine</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Morphology, Physiology and Stomatology, Faculty of Odontology of Ribeirão Preto, University of São Paulo, Brazil, Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fernandez</LastName><ForeName>Claudio O</ForeName><Initials>CO</Initials><AffiliationInfo><Affiliation>Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Papy-Garcia</LastName><ForeName>Dulce</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Laboratoire Croissance, Réparation et Régénération Tissulaires (CRRET), CNRS ERL 9215, Université Paris Est Créteil, Université Paris Est, F-94000, Créteil, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Itri</LastName><ForeName>Rosangela</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Instituto de Física da Universidade de São Paulo - IFUSP, Rua do Matão, Travessa R, 187, São Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raisman-Vozari</LastName><ForeName>Rita</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institut National De La Santé Et De La Recherche Médicale, U 1127, CNRS, Unité Mixte De Recherche (UMR) 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau Et De La Moelle Epinière, ICM, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chehín</LastName><ForeName>Rosana N</ForeName><Initials>RN</Initials><AffiliationInfo><Affiliation>Instituto Superior de Investigaciones Biológicas (INSIBIO), CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT), Chacabuco 461 (T4000ILI) Tucumán, Argentina.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>02</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>09</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>12</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>2</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28155912</ArticleId><ArticleId IdType="pii">srep41755</ArticleId><ArticleId IdType="doi">10.1038/srep41755</ArticleId><ArticleId IdType="pmc">PMC5290535</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Argentine</li><li>Brésil</li><li>France</li></country><region><li>État de São Paulo</li><li>Île-de-France</li></region><settlement><li>Créteil</li><li>Paris</li><li>São Paulo</li></settlement><orgName><li>Université de São Paulo</li></orgName></list><tree><country name="Argentine"><noRegion><name sortKey="Gonzalez Lizarraga, Florencia" sort="Gonzalez Lizarraga, Florencia" uniqKey="Gonzalez Lizarraga F" first="Florencia" last="González-Lizárraga">Florencia González-Lizárraga</name></noRegion><name sortKey="Avila, Cesar L" sort="Avila, Cesar L" uniqKey="Avila C" first="César L" last="Ávila">César L. Ávila</name><name sortKey="Binolfi, Andres" sort="Binolfi, Andres" uniqKey="Binolfi A" first="Andres" last="Binolfi">Andres Binolfi</name><name sortKey="Chehin, Rosana N" sort="Chehin, Rosana N" uniqKey="Chehin R" first="Rosana N" last="Chehín">Rosana N. Chehín</name><name sortKey="Fernandez, Claudio O" sort="Fernandez, Claudio O" uniqKey="Fernandez C" first="Claudio O" last="Fernandez">Claudio O. Fernandez</name><name sortKey="Socias, Sergio B" sort="Socias, Sergio B" uniqKey="Socias S" first="Sergio B" last="Socías">Sergio B. Socías</name><name sortKey="Torres Bugeau, Clarisa M" sort="Torres Bugeau, Clarisa M" uniqKey="Torres Bugeau C" first="Clarisa M" last="Torres-Bugeau">Clarisa M. Torres-Bugeau</name></country><country name="Brésil"><region name="État de São Paulo"><name sortKey="Barbosa, Leandro R S" sort="Barbosa, Leandro R S" uniqKey="Barbosa L" first="Leandro R S" last="Barbosa">Leandro R S. Barbosa</name></region><name sortKey="Del Bel, Elaine" sort="Del Bel, Elaine" uniqKey="Del Bel E" first="Elaine" last="Del-Bel">Elaine Del-Bel</name><name sortKey="Itri, Rosangela" sort="Itri, Rosangela" uniqKey="Itri R" first="Rosangela" last="Itri">Rosangela Itri</name></country><country name="France"><region name="Île-de-France"><name sortKey="Sepulveda Diaz, Julia E" sort="Sepulveda Diaz, Julia E" uniqKey="Sepulveda Diaz J" first="Julia E" last="Sepúlveda-Díaz">Julia E. Sepúlveda-Díaz</name></region><name sortKey="Papy Garcia, Dulce" sort="Papy Garcia, Dulce" uniqKey="Papy Garcia D" first="Dulce" last="Papy-Garcia">Dulce Papy-Garcia</name><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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