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dc.contributor.authorVarela, Juan A
dc.contributor.authorRodrigues, Margarida
dc.contributor.authorDe, Suman
dc.contributor.authorFlagmeier, Patrick
dc.contributor.authorGandhi, Sonia
dc.contributor.authorDobson, Christopher M
dc.contributor.authorKlenerman, David
dc.contributor.authorLee, Steven F
dc.date.accessioned2018-12-11T17:30:07Z
dc.date.available2018-12-11T17:30:07Z
dc.date.issued2018-04-23
dc.identifier.citationVarela , J A , Rodrigues , M , De , S , Flagmeier , P , Gandhi , S , Dobson , C M , Klenerman , D & Lee , S F 2018 , ' Optical structural analysis of individual α-synuclein oligomers ' , Angewandte Chemie International Edition , vol. 57 , no. 18 , pp. 4886-4890 . https://doi.org/10.1002/anie.201710779en
dc.identifier.issn1433-7851
dc.identifier.otherPURE: 256889341
dc.identifier.otherPURE UUID: b3110c7d-f7b9-4408-95c4-89692d3a8f29
dc.identifier.otherPubMed: 29342318
dc.identifier.otherPubMedCentral: PMC5988047
dc.identifier.otherScopus: 85044225059
dc.identifier.otherORCID: /0000-0003-1901-1378/work/51700173
dc.identifier.urihttp://hdl.handle.net/10023/16665
dc.descriptionThis study is supported by the Michael J. Fox Foundation (10200); The Royal Society with a University Research Fellowship (UF120277) (S.F.L.); a Marie‐Curie Individual Fellowship (S.D.); the Boehringer Ingelheim Fonds (P.F.), the Studienstiftung des Deutschen Volkes (P.F.); the UK Biotechnology and Biological Sciences Research Council (C.M.D.); the Wellcome Trust (C.M.D.); the Cambridge Centre for Misfolding Diseases (P.F. and C.M.D.), and the Royal Society and the European Research Council with an ERC Advanced Grant (669237) (D.K.).en
dc.description.abstractSmall aggregates of misfolded proteins play a key role in neurodegenerative disorders. Such species have proved difficult to study due to the lack of suitable methods capable of resolving these heterogeneous aggregates, which are smaller than the optical diffraction limit. We demonstrate here an all-optical fluorescence microscopy method to characterise the structure of individual protein aggregates based on the fluorescence anisotropy of dyes such as thioflavin-T, and show that this technology is capable of studying oligomers in human biofluids such as cerebrospinal fluid. We first investigated in vitro the structural changes in individual oligomers formed during the aggregation of recombinant α-synuclein. By studying the diffraction-limited aggregates we directly evaluated their structural conversion and correlated this with the potential of aggregates to disrupt lipid bilayers. We finally characterised the structural features of aggregates present in cerebrospinal fluid of Parkinson's disease patients and age-matched healthy controls.
dc.format.extent5
dc.language.isoeng
dc.relation.ispartofAngewandte Chemie International Editionen
dc.rightsCopyright © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectAmyloid fibrilsen
dc.subjectFluorescence anisotropyen
dc.subjectNeurodegenratioen
dc.subjectParkinson's diseaseen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectNDASen
dc.subject.lccRC0321en
dc.titleOptical structural analysis of individual α-synuclein oligomersen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.identifier.doihttps://doi.org/10.1002/anie.201710779
dc.description.statusPeer revieweden


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