title: α-Synuclein oligomers: an amyloid pore? Insights into mechanisms of α-synuclein oligomer-lipid interactions.
abstract: In many human diseases, oligomeric species of amyloid proteins may play a pivotal role in cytotoxicity. Many lines of evidence indicate that permeabilization of cellular membranes by amyloid oligomers may be the key factor in disrupting cellular homeostasis. However, the exact mechanisms by which the membrane integrity is impaired remain elusive. One prevailing hypothesis, the so-called amyloid pore hypothesis, assumes that annular oligomeric species embed into lipid bilayers forming transbilayer protein channels. Alternatively, an increased membrane permeability could be caused by thinning of the hydrophobic core of the lipid bilayer due to the incorporation of the oligomers between the tightly packed lipids, which would facilitate the transport of small molecules across the membrane. In this review, we briefly recapitulate our findings on the structure of α-synuclein oligomers and the factors influencing their interaction with lipid bilayers. Our results, combined with work from other groups, suggest that α-synuclein oligomers do not necessarily form pore-like structures. The emerging consensus is that local structural rearrangements of the protein lead to insertion of specific regions into the hydrophobic core of the lipid bilayer, thereby disrupting the lipid packing.
authors.affiliation: Nanobiophysics, MESA+ Institute for Nanotechnology, University of Twente, PO Box 217, 7500AE Enschede, The Netherlands.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Stöckl
authors.forename: Niels
authors.initials: N
authors.lastname: Zijlstra
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D050356:Lipid Metabolism; D011485:Protein Binding / Q000502:physiology; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D008051:Lipid Bilayers; D051844:alpha-Synuclein