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Structure, function and toxicity of alpha-synuclein: the Bermuda triangle in synucleinopathies

Lookup NU author(s): Professor Tiago OuteiroORCiD


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© 2015 International Society for NeurochemistryParkinson's disease belongs to a group of currently incurable neurodegenerative disorders characterized by the misfolding and accumulation of alpha-synuclein aggregates that are commonly known as synucleinopathies. Clinically, synucleinopathies are heterogeneous, reflecting the somewhat selective neuronal vulnerability characteristic of each disease. The precise molecular underpinnings of synucleinopathies remain unclear, but the process of aggregation of alpha-synuclein appears as a central event. However, there is still no consensus with respect to the toxic forms of alpha-synuclein, hampering our ability to use the protein as a target for therapeutic intervention. To decipher the molecular bases of synucleinopathies, it is essential to understand the complex triangle formed between the structure, function and toxicity of alpha-synuclein. Recently, important steps have been undertaken to elucidate the role of the protein in both physiological and pathological conditions. Here, we provide an overview of recent findings in the field of alpha-synuclein research, and put forward a new perspective over paradigms that persist in the field. Establishing whether alpha-synuclein has a causative role in all synucleinopathies will enable the identification of targets for the development of novel therapeutic strategies for this devastating group of disorders. (Figure presented.) Alpha-synuclein is the speculated cornerstone of several neurodegenerative disorders known as Synucleinopathies. Nevertheless, the mechanisms underlying the pathogenic effects of this protein remain unknown. Here, we review the recent findings in the three corners of alpha-synuclein biology – structure, function and toxicity – and discuss the enigmatic roads that have accompanied alpha-synuclein from the beginning. This article is part of a special issue on Parkinson disease.

Publication metadata

Author(s): Villar-Pique A, Lopes da Fonseca T, Outeiro TF

Publication type: Review

Publication status: Published

Journal: Journal of Neurochemistry

Year: 2016

Volume: 139

Issue: S1

Pages: 240-255

Print publication date: 01/10/2016

Online publication date: 11/09/2015

Acceptance date: 14/07/2015

ISSN (print): 0022-3042

ISSN (electronic): 1471-4159

Publisher: Blackwell Publishing Ltd


DOI: 10.1111/jnc.13249

PubMed id: 26190401