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Identification of novel protein phosphatases as modifiers of alpha-synuclein aggregation in yeast

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

Alpha-synuclein (aSyn) is a key player in a group of neurodegenerative diseases commonly known as synucleinopathies. Recent findings indicate phosphorylation in several aSyn residues can modulate its aggregation and subcellular localization, thereby affecting pathological processes. However, the precise molecular mechanisms governing aSyn phosphorylation are still unclear. Recent studies investigated the role of various families of protein kinases, such as the polo-like kinases, G protein-coupled receptor kinases or casein kinases. In contrast, our understanding of the phosphatases involved in the dephosphorylation of aSyn is rather limited. Here, we exploited the unique toolbox of the yeast Saccharomyces cerevisiae in order to identify novel phosphatases capable of modulating aSyn phosphorylation, inclusion formation and toxicity of human aSyn. In summary, given the association between aSyn phosphorylation and pathology in Parkinson's disease and other synucleinopathies, modulation of this post-translational modification may constitute an attractive target for therapeutic intervention.


Publication metadata

Author(s): Bras IC, Tenreiro S, Silva AM, Outeiro TF

Publication type: Article

Publication status: Published

Journal: FEMS Yeast Research

Year: 2018

Volume: 18

Issue: 8

Print publication date: 01/12/2018

Online publication date: 01/10/2018

Acceptance date: 30/09/2018

ISSN (print): 1567-1356

ISSN (electronic): 1567-1364

Publisher: Oxford University Press

URL: https://doi.org/10.1093/femsyr/foy108

DOI: 10.1093/femsyr/foy108

PubMed id: 30277516


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