Chaperone-Mediated Autophagy in Neurodegenerative Diseases: Molecular Mechanisms and Pharmacological Opportunities

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 14; p. 2250
• Main Authors: Wang, Yi-Ting, Lu, Jia-Hong
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.07.2022; MDPI
• Subjects: Aging; Alzheimer's disease; Autophagy; Cell cycle; chaperone-mediated autophagy; Degradation; Enzymes; Heat shock proteins; Homeostasis; HSC70; Hypoxia; Insects; Kinases; LAMP2A; Lipids; Lysosomes; Metabolism; Molecular modelling; Neurodegeneration; neurodegenerative disease; Neurodegenerative diseases; Oxidative stress; Parkinson's disease; Phenotypes; Physiology; Protein synthesis; Quality control; Review; Synuclein; Tau protein; α-synuclein
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11142250

Chaperone-mediated autophagy (CMA) is a protein degradation mechanism through lysosomes. By targeting the KFERQ motif of the substrate, CMA is responsible for the degradation of about 30% of cytosolic proteins, including a series of proteins associated with neurodegenerative diseases (NDs). The fact that decreased activity of CMA is observed in NDs, and ND-associated mutant proteins, including alpha-synuclein and Tau, directly impair CMA activity reveals a possible vicious cycle of CMA impairment and pathogenic protein accumulation in ND development. Given the intrinsic connection between CMA dysfunction and ND, enhancement of CMA has been regarded as a strategy to counteract ND. Indeed, genetic and pharmacological approaches to modulate CMA have been shown to promote the degradation of ND-associated proteins and alleviate ND phenotypes in multiple ND models. This review summarizes the current knowledge on the mechanism of CMA with a focus on its relationship with NDs and discusses the therapeutic potential of CMA modulation for ND.