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

Fusco, Giuliana; Chen, Serene W.; Williamson, Philip T. F.; Cascella, Roberta; Perni, Michele; Jarvis, James A.; Cecchi, Cristina; Vendruscolo, Michele; Chiti, Fabrizio; Cremades, Nunilo; Ying, Liming; Dobson, Christopher M.; Simone, Alfonso De

doi:10.1126/science.aan6160

articleScienceDec 14, 2017GREEN OA

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

GFGiuliana Fusco SWSerene W. Chen PTPhilip T. F. Williamson RCRoberta Cascella MPMichele Perni

University of Cambridge · Imperial College London · +3 more institutions

PubMed

Indexed incrossrefdatacitepubmed

Abstract

Oligomeric species populated during the aggregation process of α-synuclein have been linked to neuronal impairment in Parkinson's disease and related neurodegenerative disorders. By using solution and solid-state nuclear magnetic resonance techniques in conjunction with other structural methods, we identified the fundamental characteristics that enable toxic α-synuclein oligomers to perturb biological membranes and disrupt cellular function; these include a highly lipophilic element that promotes strong membrane interactions and a structured region that inserts into lipid bilayers and disrupts their integrity. In support of these conclusions, mutations that target the region that promotes strong membrane…

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Topics & keywords

Topics

Keywords

Toxicity
Fibril
Chemistry
Alpha-synuclein
Biophysics
Amyloid fibril
Parkinson's disease
Biochemistry

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