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Nat Rev Neurosci. 2013 Jan;14(1):38-48. doi: 10.1038/nrn3406.

The many faces of α-synuclein: from structure and toxicity to therapeutic target.

Author information

1
Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.

Abstract

Disorders characterized by α-synuclein (α-syn) accumulation, Lewy body formation and parkinsonism (and in some cases dementia) are collectively known as Lewy body diseases. The molecular mechanism (or mechanisms) through which α-syn abnormally accumulates and contributes to neurodegeneration in these disorders remains unknown. Here, we provide an overview of current knowledge and prevailing hypotheses regarding the conformational, oligomerization and aggregation states of α-syn and their role in regulating α-syn function in health and disease. Understanding the nature of the various α-syn structures, how they are formed and their relative contributions to α-syn-mediated toxicity may inform future studies aiming to develop therapeutic prevention and intervention.

PMID:
23254192
PMCID:
PMC4295774
DOI:
10.1038/nrn3406
[Indexed for MEDLINE]
Free PMC Article

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