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dc.contributor.authorGalvagnion, Celineen
dc.contributor.authorBuell, Alexanderen
dc.contributor.authorMeisl, Georgen
dc.contributor.authorMichaels, Thomasen
dc.contributor.authorVendruscolo, Micheleen
dc.contributor.authorKnowles, Tuomasen
dc.contributor.authorDobson, Christopheren
dc.date.accessioned2015-01-26T12:08:32Z
dc.date.available2015-01-26T12:08:32Z
dc.date.issued2015-02-02en
dc.identifier.citationNature Chemical Biology 11, 229–234 (2015). doi: 10.1038/nchembio.1750en
dc.identifier.issn1552-4450
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246597
dc.description.abstractα-synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity but its aggregation to form amyloid fibrils is the hallmark of Parkinson’s disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function but under other circumstances is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we have identified in this study the mechanism through which facile aggregation of α-syn is induced under conditions where it binds to a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can play in triggering conversion of α-syn from its soluble state into the aggregated state that is associated with neurodegeneration and to its associated disease states.
dc.description.sponsorshipThis work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College, Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals (CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.titleLipid vesicles trigger α-synuclein aggregation by stimulating primary nucleationen
dc.typeArticle
dc.description.versionThis is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htmlen
prism.endingPage234
prism.publicationDate2015en
prism.publicationNameNature Chemical Biologyen
prism.startingPage229
prism.volume11en
dc.rioxxterms.funderBBSRC
dc.rioxxterms.funderWellcome Trust
dcterms.dateAccepted2014-12-17en
rioxxterms.versionofrecord10.1038/nchembio.1750en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-02-02en
dc.contributor.orcidMeisl, Georg [0000-0002-6562-7715]
dc.contributor.orcidMichaels, Thomas [0000-0001-6931-5041]
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.contributor.orcidKnowles, Tuomas [0000-0002-7879-0140]
dc.identifier.eissn1552-4469
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (094425/Z/10/Z)
pubs.funder-project-idBBSRC (BB/H003843/1)
pubs.funder-project-idBBSRC (BB/J002119/1)
pubs.funder-project-idWellcome Trust (089703/Z/09/Z)
pubs.funder-project-idEuropean Research Council (337969)


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