Deficient chaperone-mediated autophagy facilitates LPS-induced microglial activation via regulation of the p300/NF-κB/NLRP3 pathway.

ABSTRACT: Neuroinflammation is a pathological change that is involved in the progression of Parkinson's disease. Dysfunction of chaperone-mediated autophagy (CMA) has proinflammatory effects. However, the mechanism by which CMA mediates inflammation and whether CMA affects microglia and microglia-mediated neuronal damage remain to be elucidated. In the present study, we found that LAMP2A, a limiting protein for CMA, was decreased in lipopolysaccharide (LPS)-treated primary microglia. Activation of CMA by the activator CA significantly repressed LPS-induced microglial activation, whereas CMA dysfunction exacerbated microglial activation. We further identified that the protein p300 was a substrate of CMA. Degradation of p300 by CMA reduced p65 acetylation, thereby inhibiting the transcription of proin

SUBMITTER: Wu J 

PROVIDER: S-EPMC10558133 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature