OTUD5 Protects Dopaminergic Neurons by Promoting the Degradation of α-Synuclein in Parkinson's Disease Model.

ABSTRACT: Defective clearance and accumulation of α-synuclein (α-Syn) is the key pathogenic factor in Parkinson's disease (PD). Recent studies emphasize the importance of E3 ligases in regulating the degradation of α-Syn. However, the molecular mechanisms by which deubiquitinases regulate α-Syn degradation are scarcely studied. In this study, it is found that the protein levels of α-Syn are negatively regulated by ovarian tumor protease deubiquitinase 5 (OTUD5) which protects dopaminergic (DA) neurons in the PD model. Mechanistically, OTUD5 promotes K63-linked polyubiquitination of α-Syn independent of its deubiquitinating enzyme activity and mediates its endolysosomal degradation by recruiting the E3 ligase neural precursor cell expressed developmentally downregulated 4 (NEDD4). Furthermore, OTUD5

SUBMITTER: Song X 

PROVIDER: S-EPMC11831440 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature