Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-58435

Reynolds, Nicholas P; Soragni, Alice; Rabe, Michael; Verdes, Dorinel; Liverani, Ennio; Handschin, Stephan; Riek, Roland; Seeger, Stefan (2011). Mechanism of membrane interaction and disruption by α-synuclein. Journal of the American Chemical Society, 133(48):19366-19375.

[img]Published Version
PDF - Registered users only
View at publisher
Accepted Version


Parkinson's disease is a common progressive neurodegenerative condition, characterized by the deposition of amyloid fibrils as Lewy bodies in the substantia nigra of affected individuals. These insoluble aggregates predominantly consist of the protein α-synuclein. There is increasing evidence suggesting that the aggregation of α-synuclein is influenced by lipid membranes and, vice versa, the membrane integrity is severely affected by the presence of bound aggregates. Here, using the surface-sensitive imaging technique supercritical angle fluorescence microscopy and Förster resonance energy transfer, we report the direct observation of α-synuclein aggregation on supported lipid bilayers. Both the wild-type and the two mutant forms of α-synuclein studied, namely, the familiar variant A53T and the designed highly toxic variant E57K, were found to follow the same mechanism of polymerization and membrane damage. This mechanism involved the extraction of lipids from the bilayer and their clustering around growing α-synuclein aggregates. Despite all three isoforms following the same pathway, the extent of aggregation and their effect on the bilayers was seen to be variant and concentration dependent. Both A53T and E57K formed cross-β-sheet aggregates and damaged the membrane at submicromolar concentrations. The wild-type also formed aggregates in this range; however, the extent of membrane disruption was greatly reduced. The process of membrane damage could resemble part of the yet poorly understood cellular toxicity phenomenon in vivo.


60 citations in Web of Science®
61 citations in Scopus®
Google Scholar™



96 downloads since deposited on 07 Mar 2012
23 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Date:6 October 2011
Deposited On:07 Mar 2012 16:55
Last Modified:05 Apr 2016 15:34
Publisher:American Chemical Society
Additional Information:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/ja2029848
Publisher DOI:10.1021/ja2029848
PubMed ID:21978222

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page