期刊
FEBS LETTERS
卷 589, 期 19, 页码 2661-2667出版社
WILEY
DOI: 10.1016/j.febslet.2015.08.013
关键词
Parkinson's disease; alpha-Synuclein; Oligomer; Amyloid; Membranes; Laurdan fluorescence; Multiphoton microscopy; Membrane phase separation
资金
- Independent Danish Research Council, Medical Sciences
- SapereAude grant
- Department of Drug Design and Pharmacology, University of Copenhagen
- Novo Nordisk Fonden [NNF13OC0006661] Funding Source: researchfish
Oligomeric species formed during alpha-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 alpha-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 alpha-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 alpha-synuclein. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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