ParkinsonFranceV1, Hal, Checkpoint, bibRecord, 000156

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.

Identifieur interne : 000156 ( Hal/Checkpoint ); précédent : 000155; suivant : 000157

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.

Auteurs : W. Peelaerts [Belgique] ; Luc Bousset [France] ; A. Van Der Perren [France] ; A. Moskalyuk [Belgique] ; R. Pulizzi [Belgique] ; M. Giugliano [Belgique] ; C. Van Den Haute [Belgique] ; Ronald Melki [France] ; V. Baekelandt [Belgique]

Source :

Nature [ 0028-0836 ] ; 2015-06-18.

RBID : Hal:hal-01165561

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.

Url:

https://hal.archives-ouvertes.fr/hal-01165561

DOI: 10.1038/nature14547

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Le document en format XML

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<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>
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<hal api="V3">          <titleStmt>            <title xml:lang="en">α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.</title>
            <author role="aut">              <persName>                <forename type="first">W</forename>
                <surname>Peelaerts</surname>
              </persName>
              <idno type="halauthorid">1179074</idno>
              <affiliation ref="#struct-421650"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Luc</forename>
                <surname>Bousset</surname>
              </persName>
              <idno type="halauthorid">190085</idno>
              <affiliation ref="#struct-418266"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">A</forename>
                <surname>Van der Perren</surname>
              </persName>
              <idno type="halauthorid">1179076</idno>
              <affiliation ref="#struct-418266"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">A</forename>
                <surname>Moskalyuk</surname>
              </persName>
              <idno type="halauthorid">1179077</idno>
              <affiliation ref="#struct-421651"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">R</forename>
                <surname>Pulizzi</surname>
              </persName>
              <idno type="halauthorid">1179078</idno>
              <affiliation ref="#struct-421651"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">M</forename>
                <surname>Giugliano</surname>
              </persName>
              <idno type="halauthorid">1179079</idno>
              <affiliation ref="#struct-421651"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">C</forename>
                <surname>Van den Haute</surname>
              </persName>
              <idno type="halauthorid">1179080</idno>
              <affiliation ref="#struct-421650"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Ronald</forename>
                <surname>Melki</surname>
              </persName>
              <idno type="halauthorid">190086</idno>
              <affiliation ref="#struct-418266"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">V</forename>
                <surname>Baekelandt</surname>
              </persName>
              <idno type="halauthorid">1179082</idno>
              <affiliation ref="#struct-421650"></affiliation>
            </author>
            <editor role="depositor">              <persName>                <forename>Alain</forename>
                <surname>PERIGNON</surname>
              </persName>
              <email type="md5">0915a8bc0b5a494fc86eb9724296445c</email>
              <email type="domain">cnrs.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>            <edition n="v1" type="current">              <date type="whenSubmitted">2015-06-19 14:11:32</date>
              <date type="whenModified">2017-02-17 15:30:38</date>
              <date type="whenReleased">2015-06-19 14:11:32</date>
              <date type="whenProduced">2015-06-18</date>
            </edition>
            <respStmt>              <resp>contributor</resp>
              <name key="108746">                <persName>                  <forename>Alain</forename>
                  <surname>PERIGNON</surname>
                </persName>
                <email type="md5">0915a8bc0b5a494fc86eb9724296445c</email>
                <email type="domain">cnrs.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>            <distributor>CCSD</distributor>
            <idno type="halId">hal-01165561</idno>
            <idno type="halUri">https://hal.archives-ouvertes.fr/hal-01165561</idno>
            <idno type="halBibtex">peelaerts:hal-01165561</idno>
            <idno type="halRefHtml">Nature, Nature Publishing Group, 2015, 522 (7556), pp.340-4. <10.1038/nature14547></idno>
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          </publicationStmt>
          <seriesStmt>            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="UNIV-PSUD-SACLAY" p="UNIV-PARIS-SACLAY">Université Paris Sud pour Paris Saclay</idno>
          </seriesStmt>
          <notesStmt>            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>            <biblStruct>              <analytic>                <title xml:lang="en">α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.</title>
                <author role="aut">                  <persName>                    <forename type="first">W</forename>
                    <surname>Peelaerts</surname>
                  </persName>
                  <idno type="halauthorid">1179074</idno>
                  <affiliation ref="#struct-421650"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Luc</forename>
                    <surname>Bousset</surname>
                  </persName>
                  <idno type="halauthorid">190085</idno>
                  <affiliation ref="#struct-418266"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">A</forename>
                    <surname>Van der Perren</surname>
                  </persName>
                  <idno type="halauthorid">1179076</idno>
                  <affiliation ref="#struct-418266"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">A</forename>
                    <surname>Moskalyuk</surname>
                  </persName>
                  <idno type="halauthorid">1179077</idno>
                  <affiliation ref="#struct-421651"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">R</forename>
                    <surname>Pulizzi</surname>
                  </persName>
                  <idno type="halauthorid">1179078</idno>
                  <affiliation ref="#struct-421651"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">M</forename>
                    <surname>Giugliano</surname>
                  </persName>
                  <idno type="halauthorid">1179079</idno>
                  <affiliation ref="#struct-421651"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">C</forename>
                    <surname>Van den Haute</surname>
                  </persName>
                  <idno type="halauthorid">1179080</idno>
                  <affiliation ref="#struct-421650"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Ronald</forename>
                    <surname>Melki</surname>
                  </persName>
                  <idno type="halauthorid">190086</idno>
                  <affiliation ref="#struct-418266"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">V</forename>
                    <surname>Baekelandt</surname>
                  </persName>
                  <idno type="halauthorid">1179082</idno>
                  <affiliation ref="#struct-421650"></affiliation>
                </author>
              </analytic>
              <monogr>                <idno type="halJournalId" status="VALID">7333</idno>
                <idno type="issn">0028-0836</idno>
                <idno type="eissn">1476-4679</idno>
                <title level="j">Nature</title>
                <imprint>                  <publisher>Nature Publishing Group</publisher>
                  <biblScope unit="volume">522</biblScope>
                  <biblScope unit="issue">7556</biblScope>
                  <biblScope unit="pp">340-4</biblScope>
                  <date type="datePub">2015-06-18</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1038/nature14547</idno>
              <idno type="pubmed">26061766</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>            <langUsage>              <language ident="en">English</language>
            </langUsage>
            <textClass>              <classCode scheme="halDomain" n="sdv.neu.nb">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology</classCode>
              <classCode scheme="halDomain" n="sdv.neu.pc">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior</classCode>
              <classCode scheme="halDomain" n="sdv.neu.sc">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
            </textClass>
            <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.</abstract>
          </profileDesc>
        </hal>
</record>

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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.

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