Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes
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Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes. / van Maarschalkerweerd, Andreas; Vetri, Valeria; Vestergaard, Bente.
In: FEBS Letters, Vol. 589, No. 19 Pt B, 14.09.2015, p. 2661-7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes
AU - van Maarschalkerweerd, Andreas
AU - Vetri, Valeria
AU - Vestergaard, Bente
N1 - Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
PY - 2015/9/14
Y1 - 2015/9/14
N2 - 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.
AB - 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.
KW - 2-Naphthylamine
KW - Cell Membrane
KW - Cholesterol
KW - Fluorescent Dyes
KW - Laurates
KW - Protein Binding
KW - Protein Multimerization
KW - Protein Structure, Secondary
KW - alpha-Synuclein
U2 - 10.1016/j.febslet.2015.08.013
DO - 10.1016/j.febslet.2015.08.013
M3 - Journal article
C2 - 26297828
VL - 589
SP - 2661
EP - 2667
JO - F E B S Letters
JF - F E B S Letters
SN - 0014-5793
IS - 19 Pt B
ER -
ID: 161854609