α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.
Identifieur interne : 001740 ( Ncbi/Merge ); précédent : 001739; suivant : 001741α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.
Auteurs : W. Peelaerts [Belgique] ; L. Bousset [France] ; A. Van Der Perren [Belgique] ; A. Moskalyuk [Belgique] ; R. Pulizzi [Belgique] ; M. Giugliano [Belgique] ; C. Van Den Haute [Belgique] ; R. Melki [France] ; V. Baekelandt [Belgique]Source :
- Nature [ 1476-4687 ] ; 2015.
English descriptors
- KwdEn :
- Animals, Blood-Brain Barrier, Brain (drug effects), Brain (metabolism), Female, Humans, Lewy Body Disease (chemically induced), Lewy Body Disease (metabolism), Lewy Body Disease (pathology), Multiple System Atrophy (chemically induced), Multiple System Atrophy (metabolism), Multiple System Atrophy (pathology), Parkinson Disease (metabolism), Parkinson Disease (pathology), Phenotype, Rats, Rats, Wistar, Substantia Nigra (drug effects), Substantia Nigra (metabolism), Substantia Nigra (pathology), Synapses (metabolism), Synapses (pathology), alpha-Synuclein (administration & dosage), alpha-Synuclein (chemistry), alpha-Synuclein (classification), alpha-Synuclein (toxicity).
- MESH :
- chemical , administration & dosage : alpha-Synuclein.
- chemically induced : Lewy Body Disease, Multiple System Atrophy.
- chemical , chemistry : alpha-Synuclein.
- chemical , classification : alpha-Synuclein.
- drug effects : Brain, Substantia Nigra.
- metabolism : Brain, Lewy Body Disease, Multiple System Atrophy, Parkinson Disease, Substantia Nigra, Synapses.
- pathology : Lewy Body Disease, Multiple System Atrophy, Parkinson Disease, Substantia Nigra, Synapses.
- chemical , toxicity : alpha-Synuclein.
- Animals, Blood-Brain Barrier, Female, Humans, Phenotype, Rats, Rats, Wistar.
Abstract
Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson's disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.
DOI: 10.1038/nature14547
PubMed: 26061766
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Van Den Haute</name><affiliation wicri:level="3"><nlm:affiliation>1] KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium [2] KU Leuven, Leuven Viral Vector Core, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>1] KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium [2] KU Leuven, Leuven Viral Vector Core, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Melki, R" sort="Melki, R" uniqKey="Melki R" first="R" last="Melki">R. 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Peelaerts</name><affiliation wicri:level="3"><nlm:affiliation>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Bousset, L" sort="Bousset, L" uniqKey="Bousset L" first="L" last="Bousset">L. Bousset</name><affiliation wicri:level="3"><nlm:affiliation>Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Gif-sur-Yvette</settlement></placeName></affiliation></author><author><name sortKey="Van Der Perren, A" sort="Van Der Perren, A" uniqKey="Van Der Perren A" first="A" last="Van Der Perren">A. Van Der Perren</name><affiliation wicri:level="3"><nlm:affiliation>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Moskalyuk, A" sort="Moskalyuk, A" uniqKey="Moskalyuk A" first="A" last="Moskalyuk">A. Moskalyuk</name><affiliation wicri:level="4"><nlm:affiliation>Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region>Région flamande</region><region type="district" nuts="2">Province d'Anvers</region></placeName></affiliation></author><author><name sortKey="Pulizzi, R" sort="Pulizzi, R" uniqKey="Pulizzi R" first="R" last="Pulizzi">R. Pulizzi</name><affiliation wicri:level="4"><nlm:affiliation>Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region>Région flamande</region><region type="district" nuts="2">Province d'Anvers</region></placeName></affiliation></author><author><name sortKey="Giugliano, M" sort="Giugliano, M" uniqKey="Giugliano M" first="M" last="Giugliano">M. Giugliano</name><affiliation wicri:level="4"><nlm:affiliation>1] Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium [2] Department of Computer Science, University of Sheffield, S1 4DP Sheffield, UK [3] Brain Mind Institute, Swiss Federal Institute of Technology of Lausanne, 1015 Lausanne, Switzerland [4] Neuro-Electronics Research Flanders (NERF), 3001 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>1] Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium [2] Department of Computer Science, University of Sheffield, S1 4DP Sheffield, UK [3] Brain Mind Institute, Swiss Federal Institute of Technology of Lausanne, 1015 Lausanne, Switzerland [4] Neuro-Electronics Research Flanders (NERF), 3001 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="town">Heverlee</settlement><settlement type="city">Louvain</settlement></placeName><orgName type="university">Université d'Anvers</orgName></affiliation></author><author><name sortKey="Van Den Haute, C" sort="Van Den Haute, C" uniqKey="Van Den Haute C" first="C" last="Van Den Haute">C. Van Den Haute</name><affiliation wicri:level="3"><nlm:affiliation>1] KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium [2] KU Leuven, Leuven Viral Vector Core, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>1] KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium [2] KU Leuven, Leuven Viral Vector Core, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Melki, R" sort="Melki, R" uniqKey="Melki R" first="R" last="Melki">R. Melki</name><affiliation wicri:level="3"><nlm:affiliation>Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Gif-sur-Yvette</settlement></placeName></affiliation></author><author><name sortKey="Baekelandt, V" sort="Baekelandt, V" uniqKey="Baekelandt V" first="V" last="Baekelandt">V. Baekelandt</name><affiliation wicri:level="3"><nlm:affiliation>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author></analytic><series><title level="j">Nature</title><idno type="eISSN">1476-4687</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Blood-Brain Barrier</term><term>Brain (drug effects)</term><term>Brain (metabolism)</term><term>Female</term><term>Humans</term><term>Lewy Body Disease (chemically induced)</term><term>Lewy Body Disease (metabolism)</term><term>Lewy Body Disease (pathology)</term><term>Multiple System Atrophy (chemically induced)</term><term>Multiple System Atrophy (metabolism)</term><term>Multiple System Atrophy (pathology)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Phenotype</term><term>Rats</term><term>Rats, Wistar</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (metabolism)</term><term>Substantia Nigra (pathology)</term><term>Synapses (metabolism)</term><term>Synapses (pathology)</term><term>alpha-Synuclein (administration & dosage)</term><term>alpha-Synuclein (chemistry)</term><term>alpha-Synuclein (classification)</term><term>alpha-Synuclein (toxicity)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Lewy Body Disease</term><term>Multiple System Atrophy</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="classification" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Lewy Body Disease</term><term>Multiple System Atrophy</term><term>Parkinson Disease</term><term>Substantia Nigra</term><term>Synapses</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lewy Body Disease</term><term>Multiple System Atrophy</term><term>Parkinson Disease</term><term>Substantia Nigra</term><term>Synapses</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blood-Brain Barrier</term><term>Female</term><term>Humans</term><term>Phenotype</term><term>Rats</term><term>Rats, Wistar</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson's disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26061766</PMID><DateCreated><Year>2015</Year><Month>06</Month><Day>18</Day></DateCreated><DateCompleted><Year>2015</Year><Month>07</Month><Day>13</Day></DateCompleted><DateRevised><Year>2016</Year><Month>05</Month><Day>09</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-4687</ISSN><JournalIssue CitedMedium="Internet"><Volume>522</Volume><Issue>7556</Issue><PubDate><Year>2015</Year><Month>Jun</Month><Day>18</Day></PubDate></JournalIssue><Title>Nature</Title><ISOAbbreviation>Nature</ISOAbbreviation></Journal><ArticleTitle>α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.</ArticleTitle><Pagination><MedlinePgn>340-4</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/nature14547</ELocationID><Abstract><AbstractText>Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson's disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Peelaerts</LastName><ForeName>W</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bousset</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van der Perren</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moskalyuk</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pulizzi</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giugliano</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>1] Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium [2] Department of Computer Science, University of Sheffield, S1 4DP Sheffield, UK [3] Brain Mind Institute, Swiss Federal Institute of Technology of Lausanne, 1015 Lausanne, Switzerland [4] Neuro-Electronics Research Flanders (NERF), 3001 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van den Haute</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>1] KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium [2] KU Leuven, Leuven Viral Vector Core, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Melki</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baekelandt</LastName><ForeName>V</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>06</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nature</MedlineTA><NlmUniqueID>0410462</NlmUniqueID><ISSNLinking>0028-0836</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051844">alpha-Synuclein</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Nature. 2015 Jun 18;522(7556):296-7</RefSource><PMID Version="1">26061764</PMID></CommentsCorrections><CommentsCorrections RefType="CommentIn"><RefSource>Mov Disord. 2015 Nov;30(13):1727</RefSource><PMID Version="1">26769458</PMID></CommentsCorrections><CommentsCorrections RefType="CommentIn"><RefSource>Nat Rev Neurol. 2015 Aug;11(8):428</RefSource><PMID Version="1">26149979</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001812" MajorTopicYN="N">Blood-Brain Barrier</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020961" MajorTopicYN="N">Lewy Body Disease</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019578" MajorTopicYN="N">Multiple System Atrophy</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010641" MajorTopicYN="N">Phenotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013378" MajorTopicYN="N">Substantia Nigra</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013569" MajorTopicYN="N">Synapses</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051844" MajorTopicYN="N">alpha-Synuclein</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000145" MajorTopicYN="N">classification</QualifierName><QualifierName UI="Q000633" MajorTopicYN="Y">toxicity</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>03</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>05</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>6</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>6</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>7</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26061766</ArticleId><ArticleId IdType="pii">nature14547</ArticleId><ArticleId IdType="doi">10.1038/nature14547</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Belgique</li><li>France</li></country><region><li>Province d'Anvers</li><li>Province du Brabant flamand</li><li>Région flamande</li><li>Île-de-France</li></region><settlement><li>Anvers</li><li>Gif-sur-Yvette</li><li>Heverlee</li><li>Louvain</li></settlement><orgName><li>Université d'Anvers</li></orgName></list><tree><country name="Belgique"><region name="Province du Brabant flamand"><name sortKey="Peelaerts, W" sort="Peelaerts, W" uniqKey="Peelaerts W" first="W" last="Peelaerts">W. Peelaerts</name></region><name sortKey="Baekelandt, V" sort="Baekelandt, V" uniqKey="Baekelandt V" first="V" last="Baekelandt">V. Baekelandt</name><name sortKey="Giugliano, M" sort="Giugliano, M" uniqKey="Giugliano M" first="M" last="Giugliano">M. Giugliano</name><name sortKey="Moskalyuk, A" sort="Moskalyuk, A" uniqKey="Moskalyuk A" first="A" last="Moskalyuk">A. Moskalyuk</name><name sortKey="Pulizzi, R" sort="Pulizzi, R" uniqKey="Pulizzi R" first="R" last="Pulizzi">R. Pulizzi</name><name sortKey="Van Den Haute, C" sort="Van Den Haute, C" uniqKey="Van Den Haute C" first="C" last="Van Den Haute">C. Van Den Haute</name><name sortKey="Van Der Perren, A" sort="Van Der Perren, A" uniqKey="Van Der Perren A" first="A" last="Van Der Perren">A. Van Der Perren</name></country><country name="France"><region name="Île-de-France"><name sortKey="Bousset, L" sort="Bousset, L" uniqKey="Bousset L" first="L" last="Bousset">L. Bousset</name></region><name sortKey="Melki, R" sort="Melki, R" uniqKey="Melki R" first="R" last="Melki">R. Melki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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