Autophagic stress activates distinct compensatory secretory pathways in neurons.

ABSTRACT: Autophagic dysfunction is a hallmark of neurodegenerative disease, leaving neurons vulnerable to the accumulation of damaged organelles and proteins. However, the late onset of diseases suggests that compensatory quality control mechanisms may be engaged to delay the deleterious effects induced by compromised autophagy. Neurons expressing common familial Parkinson's disease (PD)-associated mutations in LRRK2 kinase exhibit defective autophagy. Here, we demonstrate that both primary murine neurons and human iPSC-derived neurons harboring pathogenic LRRK2 upregulate the secretion of extracellular vesicles. We used unbiased proteomics to characterize the secretome of LRRK2^G2019S neurons and found that autophagic cargos including mitochondrial proteins were enriched. Based on these

SUBMITTER: Palumbos SD 

PROVIDER: S-EPMC11580983 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature