biostudies-literatureWhiten DRChrist’s College, Cambridge, UKCambridge Centre for Misfolding DiseasesFondazione Umberto VeronesiHerchel Smith fellowshipRoyal SocietyUK Biotechnology and Biochemical Sciences Research CouncilAustralian Research CouncilAustralian Postgraduate AwardEuropean Research CouncilMedical Research CouncilWellcome TrustBoehringer Ingelheim FondsMarie Curie3492-3500https://www.ebi.ac.uk/biostudies/studies/S-EPMC6024880biostudies-literatureUnknown23(12)The aberrant aggregation of α-synuclein is associated with several human diseases, collectively termed the α-synucleinopathies, which includes Parkinson's disease. The progression of these diseases is, in part, mediated by extracellular α-synuclein oligomers that may exert effects through several mechanisms, including prion-like transfer, direct cytotoxicity, and pro-inflammatory actions. In this study, we show that two abundant extracellular chaperones, clusterin and α₂-macroglobulin, directly bind to exposed hydrophobic regions on the surface of α-synuclein oligomers. Using single-molecule fluorescence techniques, we found that clusterin, unlike α₂-macroglobulin, exhibits differential binding to α-synuclein oligomers that may be related to structural differences betCell reportsSingle-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic α-Synuclein Oligomers.PMC6024880DP160100011669237UKDRI-2003Tosatto LFlagmeier PDobson CMCox DDe STaylor CGWhiten DRWilson MREcroyd HKumita JRHorrocks MHKlenerman DfalseSingle-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic α-Synuclein Oligomers.The aberrant aggregation of α-synuclein is associated with several human diseases, collectively termed the α-synucleinopathies, which includes Parkinson's disease. The progression of these diseases is, in part, mediated by extracellular α-synuclein oligomers that may exert effects through several mechanisms, including prion-like transfer, direct cytotoxicity, and pro-inflammatory actions. In this study, we show that two abundant extracellular chaperones, clusterin and α₂-macroglobulin, directly bind to exposed hydrophobic regions on the surface of α-synuclein oligomers. Using single-molecule fluorescence techniques, we found that clusterin, unlike α₂-macroglobulin, exhibits differential binding to α-synuclein oligomers that may be related to structural differences bet2018-01-01T00:00:00Z2018 Jun2025-04-25T21:16:07.419Z2019-03-26T23:44:43ZS-EPMC60248802992499310.1016/j.celrep.2018.05.074