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. 2015 Jul 23;31(4):452–458. doi: 10.1007/s12264-015-1540-x

Chaperone-mediated autophagy: roles in neuroprotection

Zhibiao Cai 1, Weijun Zeng 1, Kai Tao 1, E Zhen 1, Bao Wang 1, Qian Yang 1,✉
PMCID: PMC5563711  PMID: 26206599

Abstract

Chaperone-mediated autophagy (CMA), one of the main pathways of lysosomal proteolysis, is characterized by the selective targeting and direct translocation into the lysosomal lumen of substrate proteins containing a targeting motif biochemically related to the pentapeptide KFERQ. Along with the other two lysosomal pathways, macro- and micro-autophagy, CMA is essential for maintaining cellular homeostasis and survival by selectively degrading misfolded, oxidized, or damaged cytosolic proteins. CMA plays an important role in pathologies such as cancer, kidney disorders, and neurodegenerative diseases. Neurons are post-mitotic and highly susceptible to dysfunction of cellular quality-control systems. Maintaining a balance between protein synthesis and degradation is critical for neuronal functions and homeostasis. Recent studies have revealed several new mechanisms by which CMA protects neurons through regulating factors critical for their viability and homeostasis. In the current review, we summarize recent advances in the understanding of the regulation and physiology of CMA with a specifi c focus on its possible roles in neuroprotection.

Keywords: chaperone-mediated autophagy, cellular homeostasis, neuroprotection, neuronal death, neurodegenerative disease

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