Reference: Auluck PK, et al. (2010) α-Synuclein: Membrane Interactions and Toxicity in Parkinson's Disease. Annu Rev Cell Dev Biol 26:211-33

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Abstract

In the late 1990s, mutations in the synaptic protein alpha-synuclein (alpha-syn) were identified in families with hereditary Parkinson's disease (PD). Rapidly, alpha-syn became the target of numerous investigations that have transformed our understanding of the pathogenesis underlying this disorder. alpha-Syn is the major component of Lewy bodies (LBs), cytoplasmic protein aggregates that form in the neurons of PD patients. alpha-Syn interacts with lipid membranes and adopts amyloid conformations that deposit within LBs. Work in yeast and other model systems has revealed that alpha-syn-associated toxicity might be the consequence of abnormal membrane interactions and alterations in vesicle trafficking. Here we review evidence regarding alpha-syn's normal interactions with membranes and regulation of synaptic vesicles as well as how overexpression of alpha-syn yields global cellular dysfunction. Finally, we present a model linking vesicle dynamics to toxicity with the sincere hope that understanding these disease mechanisms will lead to the development of novel, potent therapeutics. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 26 is October 06, 2010. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Reference Type
Journal Article
Authors
Auluck PK, Caraveo G, Lindquist S
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