Role of autophagy and proteostasis in neurodegenerative diseases: Exploring the therapeutic interventions

Chem Biol Drug Des. 2024 Apr;103(4):e14515. doi: 10.1111/cbdd.14515.

Abstract

Neurodegenerative disorders are devastating disorders characterized by gradual loss of neurons and cognition or mobility impairment. The common pathological features of these diseases are associated with the accumulation of misfolded or aggregation of proteins. The pivotal roles of autophagy and proteostasis in maintaining cellular health and preventing the accumulation of misfolded proteins, which are associated with neurodegenerative diseases like Huntington's disease (HD), Alzheimer's disease (AD), and Parkinson's disease (PD). This article presents an in-depth examination of the interplay between autophagy and proteostasis, highlighting how these processes cooperatively contribute to cellular homeostasis and prevent pathogenic protein aggregate accumulation. Furthermore, the review emphasises the potential therapeutic implications of targeting autophagy and proteostasis to mitigate neurodegenerative diseases. While advancements in research hold promise for developing novel treatments, the article also addresses the challenges and complexities associated with modulating these intricate cellular pathways. Ultimately, advancing understanding of the underlying mechanism of autophagy and proteostasis in neurodegenerative disorders provides valuable insights into potential therapeutic avenues and future research directions.

Keywords: cellular homeostatis; neurodegenerative disorders; pathogenesis; proteostasis.

Publication types

  • Review

MeSH terms

  • Autophagy
  • Humans
  • Huntington Disease* / drug therapy
  • Huntington Disease* / metabolism
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / metabolism
  • Proteins / metabolism
  • Proteostasis

Substances

  • Proteins