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Lookup NU author(s): Professor Tiago OuteiroORCiD
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Alpha-synuclein (α-syn) is a soluble protein highly enriched in presynaptic terminals of neurons. Accumulation of α-syn as intracellular filamentous aggregates is a pathological feature of sporadic and familial forms of Parkinson's disease (PD). Changes in α-syn post-translational modifications, as well as mitochondrial dysfunction and oxidative stress constitute key pathogenic events of this disorder. Here we assessed the correlation between α-syn phosphorylation at serine 129 (Ser129), the formation of reactive oxygen species (ROS) and mitochondrial dysfunction in SH-SY5Y cells expressing A53T mutant or wild-type (WT) α-syn, exposed to ferrous iron (FeSO4) and rotenone (complex I inhibitor). Under basal conditions, prolonged expression of A53T mutant α-syn altered mitochondria morphology, increased superoxide formation and phosphorylation at Ser129, which was linked to decreased activity of protein phosphatase 2A (PP2A). Exposure to FeSO4 or rotenone enhanced intracellular ROS levels, including superoxide anions, in both types of cells, along with α-syn Ser129 phosphorylation and mitochondrial depolarization. Most of these changes were largely evident in A53T mutant α-syn expressing cells. Overall, the data suggest that stimuli that promote ROS formation and mitochondrial alterations highly correlate with mutant α-syn phosphorylation at Ser129, which may precede cell degeneration in PD. © 2014 Elsevier Inc.
Author(s): Perfeito R, Lazaro DF, Outeiro TF, Rego AC
Publication type: Article
Publication status: Published
Journal: Molecular and Cellular Neuroscience
Print publication date: 01/09/2014
Online publication date: 07/08/2014
Acceptance date: 06/08/2014
ISSN (print): 1044-7431
ISSN (electronic): 1095-9327
Publisher: Academic Press Inc.
PubMed id: 25109238
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