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Lookup NU author(s): Professor Tiago OuteiroORCiD
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© 2022 Elsevier B.V.The exon skipping of α-Synuclein (α-Syn), the main constituent of the abnormal protein aggregation in Lewy bodies of Parkinson's disease (PD), forms four isoforms. In contrast to the full length α-Syn (α-Syn 140), little is known about the splice isoforms' properties and functions. SUMOylation, a post-translational modification, regulates α-Syn function, aggregation, and degradation, but information about α-Syn isoforms and the effect of SUMOylation on them is unknown. Therefore, this study aims to characterize the SUMOylation of α-Syn isoforms and its impact on cell death and α-Syn aggregation. In a cellular model of PD induced by rotenone, cell toxicity, SUMOylation, and α-Syn aggregation with or without isoforms overexpression were evaluated. First, rotenone induced cell toxicity and α-Syn aggregation, with a significant reduction of SUMOylation and autophagy. Boosting SUMOylation prevented α-Syn aggregation, phosphorylation and recovery of autophagy. Moreover, α-Syn 140 and α-Syn 126 were SUMOylated while the other two isoforms, α-Syn 112 and 98 were not and their overexpression showed that were more toxic and induced more α-Syn aggregation. Rotenone increased their toxicity that was not affected by boosting SUMOylation. These results may indicate a role of SUMOylation in modulating α-Syn aggregation, inducing to understanding more about the behavior of α-Syn isoforms.
Author(s): Hassanzadeh K, Morrone C, Akhtari K, Gerhardt E, Zaccagnini L, Outeiro TF, Feligioni M
Publication type: Article
Publication status: Published
Journal: Mechanisms of Ageing and Development
Year: 2023
Volume: 209
Print publication date: 01/01/2023
Online publication date: 02/12/2022
Acceptance date: 29/11/2022
ISSN (print): 0047-6374
ISSN (electronic): 1872-6216
Publisher: Elsevier Ireland Ltd
URL: https://doi.org/10.1016/j.mad.2022.111759
DOI: 10.1016/j.mad.2022.111759
PubMed id: 36464085
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