Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers-Reference-Cited by-同舟云学术

Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers

Published:2017-12-15 Issue:6369 Volume:358 Page:1440-1443
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Fusco Giuliana¹²^ORCID,Chen Serene W.¹²^ORCID,Williamson Philip T. F.³^ORCID,Cascella Roberta⁴^ORCID,Perni Michele¹^ORCID,Jarvis James A.²,Cecchi Cristina⁴^ORCID,Vendruscolo Michele¹,Chiti Fabrizio⁴^ORCID,Cremades Nunilo⁵^ORCID,Ying Liming⁶^ORCID,Dobson Christopher M.¹^ORCID,De Simone Alfonso²^ORCID

Affiliation:

1. Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.

2. Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

3. Centre for Biological Sciences and Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.

4. Department of Experimental and Clinical Biomedical Sciences, Section of Biochemistry, University of Florence, 50134 Florence, Italy.

5. Biocomputation and Complex Systems Physics Institute (BIFI), Joint Unit BIFI–Instituto de Química Física “Rocasolano” (Consejo Superior de Investigaciones Científicas), University of Zaragoza, 50018 Zaragoza, Spain.

6. Molecular Medicine, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.

Abstract

A structural look at α-synuclein oligomers Fibrillar aggregates of the protein α-synuclein (αS) are the major constituents of Lewy bodies in Parkinson's disease. However, small oligomers that accumulate during the process of fibril formation are thought to cause the neuronal toxicity associated with the onset and progression of Parkinson's disease. Little is known about the detailed structural properties of αS oligomers and the molecular mechanisms that lead to their toxicity. Fusco et al. report the structural characterization of two forms of αS oligomers, which elucidates the fundamental structural elements giving rise to neuronal toxicity. Science , this issue p. 1440

Funder

Wellcome Trust

Biotechnology and Biological Sciences Research Council

British Heart Foundation

Leverhulme Trust

Centre for Misfolding Disease of the University of Cambridge

Regione Toscana FAS-Salute

Fondi di Ateneo of the University of Florence

UK Medical Research Council

Parkinson’s UK

Ministry of Economy and Competitiveness of Spain

Publisher