Autophagic stress activates distinct compensatory secretory pathways in neurons
Output Details
Preprint July 14, 2025
Description
A hallmark feature of many neurodegenerative diseases is autophagy dysfunction, resulting in the accumulation of damaged proteins and organelles that is detrimental to neuronal health. The late onset of many neurodegenerative diseases, however, suggests alternative quality control mechanisms may delay neuronal degeneration. Here, we demonstrate that neurons expressing a Parkinson’s Disease-associated mutation upregulate the release of two extracellular vesicle populations. First, we observe the increased expulsion of autophagic vesicles, which mediates cellular waste disposal. Second, we observe the increased release of exosomes, likely to facilitate transcellular communication. Thus, we propose that increases in secretory autophagy and exosome release are a homeostatic response in neurons undergoing chronic stress.
Identifier (DOI)
10.1073/pnas.2421886122
