Pharmacological Tools to Modulate Autophagy in Neurodegenerative Diseases

J Mol Biol. 2020 Apr 3;432(8):2822-2842. doi: 10.1016/j.jmb.2020.02.023. Epub 2020 Feb 24.

Abstract

Considerable evidences suggest a link between autophagy dysfunction, protein aggregation, and neurodegenerative diseases. Given that autophagy is a conserved intracellular housekeeping process, modulation of autophagy flux in various model organisms have highlighted its importance for maintaining proteostasis. In postmitotic cells such as neurons, compromised autophagy is sufficient to cause accumulation of ubiquitinated aggregates, neuronal dysfunction, degeneration, and loss of motor coordination-all hallmarks of neurodegenerative diseases. Reciprocally, enhanced autophagy flux augments cellular and organismal health, in addition to extending life span. These genetic studies not-withstanding a plethora of small molecule modulators of autophagy flux have been reported that alleviate disease symptoms in models of neurodegenerative diseases. This review summarizes the potential of such molecules to be, perhaps, one of the first autophagy drugs for treating these currently incurable diseases.

Keywords: Aggrephagy; Aggresome; Autophagy modulators; Misfolded proteins; Neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy*
  • Humans
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / pathology
  • Protein Aggregation, Pathological / prevention & control*
  • Small Molecule Libraries / pharmacology*

Substances

  • Small Molecule Libraries