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dc.contributor.authorHardenberg, Maarten Cen
dc.contributor.authorSinnige, Tessaen
dc.contributor.authorCasford, Samen
dc.contributor.authorDada, Samuel Ten
dc.contributor.authorPoudel, Chetanen
dc.contributor.authorRobinson, Elizabeth Aen
dc.contributor.authorFuxreiter, Monikaen
dc.contributor.authorKaminksi, Clemens Fen
dc.contributor.authorKaminski, Gabrieleen
dc.contributor.authorNollen, Ellen AAen
dc.contributor.authorDobson, Christopher Men
dc.contributor.authorVendruscolo, Micheleen
dc.date.accessioned2020-12-15T00:32:09Z
dc.date.available2020-12-15T00:32:09Z
dc.date.issued2021-08en
dc.identifier.issn1674-2788
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315115
dc.description.abstractMisfolded a-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson’s disease. A large body of evidence shows that a-synuclein can aggregate into amyloid fibrils, but the relationship between a-synuclein self-assembly and Lewy body formation remains unclear. Here we show, both in vitro and in a C. elegans model of Parkinson’s disease, that a-synuclein undergoes liquid-liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of a-synuclein condensates in the presence of lipids and other cellular components.
dc.description.sponsorshipWellcome Trust (065807/Z/01/Z) (203249/Z/16/Z). Also, the UK Medical Research Council (MRC) (MR/K02292X/1), Alzheimer Research UK (ARUK) (ARUK-PG013-14), Michael J Fox Foundation (16238) and from Infinitus China Ltd.
dc.format.mediumPrinten
dc.languageengen
dc.publisherOxford University Press (OUP)
dc.rightsAll rights reserved
dc.titleObservation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies.en
dc.typeArticle
prism.endingPage294
prism.issueIdentifier4en
prism.publicationDate2021en
prism.publicationNameJournal of molecular cell biologyen
prism.startingPage282
prism.volume13en
dc.identifier.doi10.17863/CAM.62222
dcterms.dateAccepted2020-10-29en
rioxxterms.versionofrecord10.1093/jmcb/mjaa075en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2021-08en
dc.contributor.orcidPoudel, Chetan [0000-0002-8512-9238]
dc.contributor.orcidKaminski, Gabriele [0000-0002-1843-2202]
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.identifier.eissn1759-4685
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (065807/Z/01/Z)
pubs.funder-project-idMRC (MR/K02292X/1)
pubs.funder-project-idWellcome Trust (203249/Z/16/Z)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (722380)
pubs.funder-project-idBBSRC (BB/M011194/1)
cam.orpheus.successMon Jan 25 12:06:08 GMT 2021 - Embargo updated*
cam.orpheus.counter3*
rioxxterms.freetoread.startdate2022-01-02


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