Roles of CMA in Neurodegenerative Diseases: Regulation of Cell Organelles Homeostasis

Neurodegenerative diseases (NDDs) pose a significant public health challenge due to the rapid aging of the global population. Common features of NDDs include the abnormal aggregation of different proteins and disruption of normal function of organelles. Chaperone-mediated autophagy (CMA), one of the main pathways of lysosomal-mediated proteolysis, selectively delivers cytosolic proteins with an exposed KFERQ-like motif into the lysosomal lumen for degradation. CMA is essential for maintaining neuronal homeostasis, and its dysfunction has been implicated in aging and NDDs. Recent studies have revealed several mechanisms by which CMA is involved in the pathogenesis of NDDs. This review summarized the current understanding of the fundamental processes and regulatory mechanisms of CMA. Furthermore, we elucidate the links between CMA and NDDs, primarily focusing on how CMA regulates the function of cellular organelles in the pathological process underlying NDDs. Targeting impaired CMA represents an attractive and promising therapeutic strategy for the treatment of NDDs.