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

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.

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology

“…Autophagy, a conserved cellular pathway, is fundamental to the maintenance of cellular homeostasis through the degradation and recycling of intracellular components ( Klionsky, 2005 ; Mizushima and Komatsu, 2011 ; Lin et al, 2024 ). It plays a critical role in various physiological processes and has been implicated in the pathology of a wide spectrum of diseases, including neurodegenerative disorders ( Liénard et al, 2024 ; Panwar et al, 2024 ) and cancer ( Mathur et al, 2024 ; Rajendran et al, 2024 ; Yang et al, 2024 ). VMP1, a transmembrane protein that orchestrates key steps in the autophagic process, from the nucleation of autophagosomes to their fusion with lysosomes for cargo degradation ( Ropolo et al, 2007 ; Mizushima and Komatsu, 2011 ; Hamasaki et al, 2013 ; Parzych and Klionsky, 2014 ; Wang et al, 2020b ; Wang et al, 2021b ; Dong et al, 2021 ; Jiang et al, 2022 ).…”