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

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 pre...

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Bibliographic Details
Published in:FEMS yeast research 2018-12, Vol.18 (8), p.1
Main Authors: Brás, Inês Caldeira, Tenreiro, Sandra, Silva, Andreia M, Outeiro, Tiago F
Format: Article
Language:English
Subjects:
alpha-Synuclein - genetics
alpha-Synuclein - metabolism
Casein
Dephosphorylation
Genetic Testing
Humans
Kinases
Localization
Membrane proteins
Molecular modelling
Movement disorders
Nervous system diseases
Neurodegenerative diseases
Neurotoxicity
Parkinson's disease
Phosphatase
Phosphatases
Phosphoprotein Phosphatases - genetics
Phosphoprotein Phosphatases - metabolism
Phosphorylation
Post-translation
Post-translational modification
Protein Aggregates
Protein Denaturation
Protein kinase
Protein kinases
Protein Multimerization
Proteins
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Synuclein
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Summary: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.
ISSN:1567-1364
1567-1356
1567-1364
DOI:10.1093/femsyr/foy108