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Alpha-synuclein: From secretion to dysfunction and death

Lookup NU author(s): Professor Tiago OuteiroORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


The aggregation, deposition, and dysfunction of alpha-synuclein (aSyn) are common events in neurodegenerative disorders known as synucleinopathies. These include Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. A growing body of knowledge on the biology of aSyn is emerging and enabling novel hypotheses to be tested. In particular, the hypothesis that aSyn is secreted from neurons, thus contributing to the spreading of pathology not only in the brain but also in other organs, is gaining momentum. Nevertheless, the precise mechanism(s) of secretion, as well as the consequences of extracellular aSyn species for neighboring cells are still unclear. Here, we review the current literature and integrate existing data in order to propose possible mechanisms of secretion, cell dysfunction, and death. Ultimately, the complete understanding of these processes might open novel avenues for the development of new therapeutic strategies. © 2012 Macmillan Publishers Limited.

Publication metadata

Author(s): Marques O, Outeiro TF

Publication type: Review

Publication status: Published

Journal: Cell Death and Disease

Year: 2012

Volume: 3

Issue: 7

Online publication date: 19/07/2012

ISSN (electronic): 2041-4889


DOI: 10.1038/cddis.2012.94

PubMed id: 22825468