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Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Oligomeric species formed during α-synuclein fibrillation are suggested to be membrane-disrupting agents, and have been associated with cytotoxicity in Parkinson's disease. The majority of studies, however, have revealed that the effect of α-synuclein oligomers is only noticeable on systems composed of anionic lipids, while the more physiologically relevant zwitterionic lipids remain intact. We present experimental evidence for significant morphological changes in zwitterionic membranes containing cholesterol, induced by α-synuclein oligomers. Depending on the lipid composition, model membranes are either unperturbed, disrupt, or undergo dramatic morphological changes and segregate into structurally different components, which we visualize by 2-photon fluorescence microscopy and generalized polarization analysis using the fluorescent probe Laurdan. Our results highlight the crucial role of cholesterol for mediating interactions between physiologically relevant membranes and α-synuclein.
OriginalsprogEngelsk
TidsskriftFEBS letters
Vol/bind589
Udgave nummer19 Pt B
Sider (fra-til)2661-7
Antal sider7
ISSN0014-5793
DOI
StatusUdgivet - 14 sep. 2015

ID: 161854609