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FEBS Lett. 2015 Sep 14;589(19 Pt B):2661-7. doi: 10.1016/j.febslet.2015.08.013. Epub 2015 Aug 20.

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

Author information

1
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
2
Dipartimento di Fisica e Chimica, Universitá di Palermo, Viale delle Scienze Ed. 18, 90128 Palermo, Italy. Electronic address: valeria.vetri@unipa.it.
3
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: Bente.Vestergaard@sund.ku.dk.

Abstract

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.

KEYWORDS:

Amyloid; Laurdan fluorescence; Membrane phase separation; Membranes; Multiphoton microscopy; Oligomer; Parkinson’s disease; α-Synuclein

PMID:
26297828
DOI:
10.1016/j.febslet.2015.08.013
[Indexed for MEDLINE]
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