Exploring the Role of Autophagy Dysfunction in Neurodegenerative Disorders

Mol Neurobiol. 2021 Oct;58(10):4886-4905. doi: 10.1007/s12035-021-02472-0. Epub 2021 Jul 2.

Abstract

Autophagy is a catabolic pathway by which misfolded proteins or damaged organelles are engulfed by autophagosomes and then transported to lysosomes for degradation. Recently, a great improvement has been done to explain the molecular mechanisms and roles of autophagy in several important cellular metabolic processes. Besides being a vital clearance pathway or a cell survival pathway in response to different stresses, autophagy dysfunction, either upregulated or down-regulated, has been suggested to be linked with numerous neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis. Impairment at different stages of autophagy results in the formation of large protein aggregates and damaged organelles, which leads to the onset and progression of different neurodegenerative disorders. This article elucidates the recent progress about the role of autophagy in neurodegenerative disorders and explains how autophagy dysfunction is linked with the pathogenesis of such disorders as well as the novel potential autophagy-associated therapies for treating them.

Keywords: Autophagosome; Autophagy; Dysfunction; Neurodegenerative disorders; Pathophysiology.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagosomes / drug effects
  • Autophagosomes / metabolism*
  • Autophagosomes / pathology
  • Autophagy / drug effects
  • Autophagy / physiology*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Lysosomes / pathology
  • MTOR Inhibitors / pharmacology
  • MTOR Inhibitors / therapeutic use
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Trehalose / pharmacology
  • Trehalose / therapeutic use

Substances

  • MTOR Inhibitors
  • Metformin
  • Trehalose