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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Targeting α-synuclein for treating Parkinson’s disease: mechanistic and therapeutic considerations</title><author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Bourdenx, Mathieu" sort="Bourdenx, Mathieu" uniqKey="Bourdenx M" first="Mathieu" last="Bourdenx">Mathieu Bourdenx</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Gorry, Philippe" sort="Gorry, Philippe" uniqKey="Gorry P" first="Philippe" last="Gorry">Philippe Gorry</name><affiliation><nlm:aff id="A2">Research Unit of Theoretical & Applied Economics, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5113, 33608 Pessac, France</nlm:aff></affiliation></author><author><name sortKey="Przedborski, Serge" sort="Przedborski, Serge" uniqKey="Przedborski S" first="Serge" last="Przedborski">Serge Przedborski</name><affiliation><nlm:aff id="A3">Departments of Neurology, Pathology and Cell Biology, and the Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Vila, Miquel" sort="Vila, Miquel" uniqKey="Vila M" first="Miquel" last="Vila">Miquel Vila</name><affiliation><nlm:aff id="A4">Neurodegenerative Diseases Research Group, Vall d’Hebron Research Institute, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas, 08035 Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><affiliation><nlm:aff id="A7">ICM, Paris, France; Sorbonne Universités</nlm:aff></affiliation><affiliation><nlm:aff id="A8">UPMC Université Paris 06, UM 75, ICM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A9">CNRS, UMR 7225, ICM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Inserm, U 1127, ICM, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name><affiliation><nlm:aff id="A11">Molecular Genetics Section and Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD20892, USA</nlm:aff></affiliation></author><author><name sortKey="Olanow, C Warren" sort="Olanow, C Warren" uniqKey="Olanow C" first="C. Warren" last="Olanow">C. Warren Olanow</name><affiliation><nlm:aff id="A12">Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Merchant, Kalpana M" sort="Merchant, Kalpana M" uniqKey="Merchant K" first="Kalpana M." last="Merchant">Kalpana M. Merchant</name><affiliation><nlm:aff id="A13">TransThera Consulting Co., Zionsville, IN, 46077, USA</nlm:aff></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Petsko, Gregory A" sort="Petsko, Gregory A" uniqKey="Petsko G" first="Gregory A." last="Petsko">Gregory A. Petsko</name><affiliation><nlm:aff id="A14">Department of Neurology and Feil Family Brain and Mind research Institute, Weill Cornell Medical College, New York NY 10021, USA</nlm:aff></affiliation></author><author><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G." last="Meissner">Wassilios G. Meissner</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26050140</idno><idno type="pmc">5217462</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217462</idno><idno type="RBID">PMC:5217462</idno><idno type="doi">10.1016/S1474-4422(15)00006-X</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000596</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000596</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Targeting α-synuclein for treating Parkinson’s disease: mechanistic and therapeutic considerations</title><author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Bourdenx, Mathieu" sort="Bourdenx, Mathieu" uniqKey="Bourdenx M" first="Mathieu" last="Bourdenx">Mathieu Bourdenx</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Gorry, Philippe" sort="Gorry, Philippe" uniqKey="Gorry P" first="Philippe" last="Gorry">Philippe Gorry</name><affiliation><nlm:aff id="A2">Research Unit of Theoretical & Applied Economics, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5113, 33608 Pessac, France</nlm:aff></affiliation></author><author><name sortKey="Przedborski, Serge" sort="Przedborski, Serge" uniqKey="Przedborski S" first="Serge" last="Przedborski">Serge Przedborski</name><affiliation><nlm:aff id="A3">Departments of Neurology, Pathology and Cell Biology, and the Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Vila, Miquel" sort="Vila, Miquel" uniqKey="Vila M" first="Miquel" last="Vila">Miquel Vila</name><affiliation><nlm:aff id="A4">Neurodegenerative Diseases Research Group, Vall d’Hebron Research Institute, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas, 08035 Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><affiliation><nlm:aff id="A7">ICM, Paris, France; Sorbonne Universités</nlm:aff></affiliation><affiliation><nlm:aff id="A8">UPMC Université Paris 06, UM 75, ICM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A9">CNRS, UMR 7225, ICM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Inserm, U 1127, ICM, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name><affiliation><nlm:aff id="A11">Molecular Genetics Section and Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD20892, USA</nlm:aff></affiliation></author><author><name sortKey="Olanow, C Warren" sort="Olanow, C Warren" uniqKey="Olanow C" first="C. Warren" last="Olanow">C. Warren Olanow</name><affiliation><nlm:aff id="A12">Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Merchant, Kalpana M" sort="Merchant, Kalpana M" uniqKey="Merchant K" first="Kalpana M." last="Merchant">Kalpana M. Merchant</name><affiliation><nlm:aff id="A13">TransThera Consulting Co., Zionsville, IN, 46077, USA</nlm:aff></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Petsko, Gregory A" sort="Petsko, Gregory A" uniqKey="Petsko G" first="Gregory A." last="Petsko">Gregory A. Petsko</name><affiliation><nlm:aff id="A14">Department of Neurology and Feil Family Brain and Mind research Institute, Weill Cornell Medical College, New York NY 10021, USA</nlm:aff></affiliation></author><author><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G." last="Meissner">Wassilios G. Meissner</name><affiliation><nlm:aff id="A1">Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</nlm:aff></affiliation></author></analytic><series><title level="j">The Lancet. Neurology</title><idno type="ISSN">1474-4422</idno><idno type="eISSN">1474-4465</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p id="P1">Progressive neuronal cell loss in a small subset of brainstem and mesencephalic nuclei and widespread aggregation of the α-synuclein protein in the form of Lewy bodies and Lewy neurites are neuropathological hallmarks of Parkinson’s disease. Most cases occur sporadically, but mutations in several genes, including α-synuclein, are associated with disease development. The mechanisms driving neurodegeneration remain unknown, hence limiting therapeutic strategies aimed at blocking neuronal death. This review describes current evidence for a predominant role of α-synuclein in the pathogenesis of PD, as well as some of the most promising α-synuclein-based strategies currently in development for this incurable neurodegenerative disorder.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101139309</journal-id><journal-id journal-id-type="pubmed-jr-id">30413</journal-id><journal-id journal-id-type="nlm-ta">Lancet Neurol</journal-id><journal-id journal-id-type="iso-abbrev">Lancet Neurol</journal-id><journal-title-group><journal-title>The Lancet. Neurology</journal-title></journal-title-group><issn pub-type="ppub">1474-4422</issn><issn pub-type="epub">1474-4465</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26050140</article-id><article-id pub-id-type="pmc">5217462</article-id><article-id pub-id-type="doi">10.1016/S1474-4422(15)00006-X</article-id><article-id pub-id-type="manuscript">NIHMS837233</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Targeting α-synuclein for treating Parkinson’s disease: mechanistic and therapeutic considerations</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Dehay</surname><given-names>Benjamin</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Bourdenx</surname><given-names>Mathieu</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gorry</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Przedborski</surname><given-names>Serge</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Vila</surname><given-names>Miquel</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Hunot</surname><given-names>Stephane</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Singleton</surname><given-names>Andrew</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Olanow</surname><given-names>C. Warren</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Merchant</surname><given-names>Kalpana M.</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Bezard</surname><given-names>Erwan</given-names></name><xref ref-type="corresp" rid="CR1">#</xref><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Petsko</surname><given-names>Gregory A.</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Meissner</surname><given-names>Wassilios G.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France</aff><aff id="A2"><label>2</label>Research Unit of Theoretical & Applied Economics, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5113, 33608 Pessac, France</aff><aff id="A3"><label>3</label>Departments of Neurology, Pathology and Cell Biology, and the Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA</aff><aff id="A4"><label>4</label>Neurodegenerative Diseases Research Group, Vall d’Hebron Research Institute, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas, 08035 Barcelona, Spain</aff><aff id="A5"><label>5</label>Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain</aff><aff id="A6"><label>6</label>Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Spain</aff><aff id="A7"><label>7</label>ICM, Paris, France; Sorbonne Universités</aff><aff id="A8"><label>8</label>UPMC Université Paris 06, UM 75, ICM, Paris, France</aff><aff id="A9"><label>9</label>CNRS, UMR 7225, ICM, Paris, France</aff><aff id="A10"><label>10</label>Inserm, U 1127, ICM, Paris, France</aff><aff id="A11"><label>11</label>Molecular Genetics Section and Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD20892, USA</aff><aff id="A12"><label>12</label>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY 10032, USA</aff><aff id="A13"><label>13</label>TransThera Consulting Co., Zionsville, IN, 46077, USA</aff><aff id="A14"><label>14</label>Department of Neurology and Feil Family Brain and Mind research Institute, Weill Cornell Medical College, New York NY 10021, USA</aff><author-notes><corresp id="CR1"><label>#</label>To whom correspondence should be addressed: Erwan Bezard, Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, Bât 3B 1er étage, 146 rue Léo Saignat, 33076 Bordeaux cedex; phone: +33 5 57 57 15 40; <email>erwan.bezard@u-bordeaux.fr</email>.
</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>20</day><month>12</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>03</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>8</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>06</day><month>1</month><year>2017</year></pub-date><volume>14</volume><issue>8</issue><fpage>855</fpage><lpage>866</lpage><pmc-comment>elocation-id from pubmed: 10.1016/S1474-4422(15)00006-X</pmc-comment>
<abstract><title>Summary</title><p id="P1">Progressive neuronal cell loss in a small subset of brainstem and mesencephalic nuclei and widespread aggregation of the α-synuclein protein in the form of Lewy bodies and Lewy neurites are neuropathological hallmarks of Parkinson’s disease. Most cases occur sporadically, but mutations in several genes, including α-synuclein, are associated with disease development. The mechanisms driving neurodegeneration remain unknown, hence limiting therapeutic strategies aimed at blocking neuronal death. This review describes current evidence for a predominant role of α-synuclein in the pathogenesis of PD, as well as some of the most promising α-synuclein-based strategies currently in development for this incurable neurodegenerative disorder.</p></abstract><kwd-group><kwd>Parkinson’s disease</kwd><kwd>α-synuclein</kwd><kwd>therapeutic strategies</kwd><kwd>pipeline</kwd><kwd>clinical trials</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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