Autophagy is an important function that mediates the degradation of intracellular proteins
and organelles. Chaperone-mediated autophagy (CMA) degrades selected proteins and has a crucial
role in cellular proteostasis under various physiological and pathological conditions. CMA dysfunction leads to the accumulation of toxic protein aggregates in the central nervous system (CNS) and
is involved in the pathogenic process of neurodegenerative diseases, including Parkinson’s disease
and Alzheimer’s disease. Previous studies have suggested that the activation of CMA to degrade
aberrant proteins can provide a neuroprotective effect in the CNS. Recent studies have shown that
CMA activity is upregulated in damaged neural tissue following acute neurological insults, such
as cerebral infarction, traumatic brain injury, and spinal cord injury. It has been also suggested
that various protein degradation mechanisms are important for removing toxic aberrant proteins
associated with secondary damage after acute neurological insults in the CNS. Therefore, enhancing
the CMA pathway may induce neuroprotective effects not only in neurogenerative diseases but
also in acute neurological insults. We herein review current knowledge concerning the biological
mechanisms involved in CMA and highlight the role of CMA in neurodegenerative diseases and
acute neurological insults. We also discuss the possibility of developing CMA-targeted therapeutic
strategies for effective treatments.
Keywords: chaperone-mediated autophagy; autophagy; LAMP2A; Hsc70; neurodegenerative disease; Parkinson’s disease; Alzheimer’s disease; traumatic brain injury; spinal cord injury; central
nervous system