Chaperone-mediated autophagy and disease: Implications for cancer and neurodegeneration

Raquel Gómez-Sintes, Esperanza Arias

Research output: Contribution to journalArticlepeer-review

Abstract

Chaperone-mediated autophagy (CMA) is a proteolytic process whereby selected intracellular proteins are degraded inside lysosomes. Owing to its selectivity, CMA participates in the modulation of specific regulatory proteins, thereby playing an important role in multiple cellular processes. Studies conducted over the last two decades have enabled the molecular characterization of this autophagic pathway and the design of specific experimental models, and have underscored the importance of CMA in a range of physiological processes beyond mere protein quality control. Those findings also indicate that decreases in CMA function with increasing age may contribute to the pathogenesis of age-associated diseases, including neurodegeneration and cancer. In the context of neurological diseases, CMA impairment is thought to contribute to the accumulation of misfolded/aggregated proteins, a process central to the pathogenesis of neurodegenerative diseases. CMA therefore constitutes a potential therapeutic target, as its induction accelerates the clearance of pathogenic proteins, promoting cell survival. More recent evidence has highlighted the important and complex role of CMA in cancer biology. While CMA induction may limit tumor development, experimental evidence also indicates that inhibition of this pathway can attenuate the growth of established tumors and improve the response to cancer therapeutics. Here, we describe and discuss the evidence supporting a role of impaired CMA function in neurodegeneration and cancer, as well as future research directions to evaluate the potential of this pathway as a target for the prevention and treatment of these diseases.

Original languageEnglish (US)
Article number101025
JournalMolecular aspects of medicine
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Keywords

  • Aggregation
  • Autophagy
  • Chaperones
  • Lysosomes
  • Protein degradation
  • Tumorigenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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