Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Haruo Kanno, Kyoichi Handa, Taishi Murakami, Toshimi Aizawa, Hiroshi Ozawa

Research output: Contribution to journalReview articlepeer-review

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1205
JournalCells
Volume11
Issue number7
DOIs
Publication statusPublished - 2022 Apr 1

Keywords

  • Alzheimer’s disease
  • autophagy
  • central nervous system
  • chaperone-mediated autophagy
  • Hsc70
  • LAMP2A
  • neurodegenerative disease
  • Parkinson’s disease
  • spinal cord injury
  • traumatic brain injury

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