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Limelight on alpha-synuclein: Pathological and mechanistic implications in neurodegeneration

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

The pathogenesis of many neurodegenerative disorders arises in association with the misfolding and accumulation of a wide variety of proteins. Much emphasis has been placed on understanding the nature of these protein accumulations, including their composition, the process by which they are formed and the physiological impact they impose at cellular and, ultimately, organismal levels. Alpha-synuclein (ASYN) is the major component of protein inclusions known as Lewy bodies and Lewy neurites, which are the typical pathological hallmarks in disorders referred to as synucleinopathies. In addition, mutations or multiplications in the gene encoding for ASYN have also been shown to cause familial cases of PD, the most common synucleinopathy. Although the precise function of ASYN remains unclear, it appears to be involved in a vast array of cellular processes. Here, we review, in depth, a spectrum of cellular and molecular mechanisms that have been implicated in synucleinopathies. Importantly, detailed understanding of the biology/pathobiology of ASYN may enable the development of novel avenues for diagnosis and/or therapeutic intervention in synucleinopathies. © 2013 -IOS Press and the authors.

Publication metadata

Author(s): Wales P, Lazaro DF, Pinho R, Outeiro TF

Publication type: Review

Publication status: Published

Journal: Journal of Parkinson's Disease

Year: 2013

Volume: 3

Issue: 4

Pages: 415-459

ISSN (print): 1877-7171

ISSN (electronic): 1877-718X

Publisher: I O S Press

URL: https://doi.org/10.3233/JPD-130216

DOI: 10.3233/JPD-130216

PubMed id: 24270242

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