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Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review)

  • Authors:
    • Jiahui Huang
    • Jiazhen Wang
  • View Affiliations

  • Published online on: October 29, 2024     https://doi.org/10.3892/mmr.2024.13378
  • Article Number: 13
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cells rely on autophagy for the degradation and recycling of damaged proteins and organelles. Chaperone-mediated autophagy (CMA) is a selective process targeting proteins for degradation through the coordinated function of molecular chaperones and the lysosome‑associated membrane protein‑2A receptor (LAMP2A), pivotal in various cellular processes from signal transduction to the modulation of cellular responses under stress. In the present review, the intricate regulatory mechanisms of CMA were elucidated through multiple signaling pathways such as retinoic acid receptor (RAR)α, AMP‑activated protein kinase (AMPK), p38‑TEEB‑NLRP3, calcium signaling‑NFAT and PI3K/AKT, thereby expanding the current understanding of CMA regulation. A comprehensive exploration of CMA's versatile roles in cellular physiology were further provided, including its involvement in maintaining protein homeostasis, regulating ferroptosis, modulating metabolic diversity and influencing cell cycle and proliferation. Additionally, the impact of CMA on disease progression and therapeutic outcomes were highlighted, encompassing neurodegenerative disorders, cancer and various organ‑specific diseases. Therapeutic strategies targeting CMA, such as drug development and gene therapy were also proposed, providing valuable directions for future clinical research. By integrating recent research findings, the present review aimed to enhance the current understanding of cellular homeostasis processes and emphasize the potential of targeting CMA in therapeutic strategies for diseases marked by CMA dysfunction.
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January-2025
Volume 31 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Huang J and Wang J: Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review). Mol Med Rep 31: 13, 2025.
APA
Huang, J., & Wang, J. (2025). Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review). Molecular Medicine Reports, 31, 13. https://doi.org/10.3892/mmr.2024.13378
MLA
Huang, J., Wang, J."Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review)". Molecular Medicine Reports 31.1 (2025): 13.
Chicago
Huang, J., Wang, J."Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review)". Molecular Medicine Reports 31, no. 1 (2025): 13. https://doi.org/10.3892/mmr.2024.13378