The E3 ligase c-Cbl modulates microglial phenotypes and contributes to Parkinson's disease pathology.

ABSTRACT: Microglial activation, particularly the polarization between classical (M1 phenotype) and alternative (M2 phenotype) states, plays pivotal roles in the immune pathogenesis of Parkinson's disease (PD), with the M1 phenotype exerting neurotoxic effects and the M2 phenotype conferring neuroprotection. Modulating microglial polarization toward the M2 phenotype holds therapeutic potential for PD. This study investigated the role of c-Cbl, an E3 ubiquitin ligase implicated in modulating microglial phenotypes and protecting dopaminergic neurons. Our findings revealed that c-Cbl^-/- mice exhibited motor deficits, reduced striatal dopamine levels, and progressive dopaminergic neuron loss in the substantia nigra (SN). Genetic ablation of c-Cbl significantly increased proinflammatory cytoki

SUBMITTER: Deng S 

PROVIDER: S-EPMC12006326 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature