The proteostasis network provides targets for neurodegeneration

Br J Pharmacol. 2019 Sep;176(18):3508-3514. doi: 10.1111/bph.14643. Epub 2019 May 23.

Abstract

The production, quality control, and degradation of proteins are a tightly controlled process necessary for cell health. In order to regulate this process, cells rely upon a network of molecular chaperone proteins that bind misfolded proteins and help them fold correctly. In addition, some molecular chaperones can target terminally misfolded proteins for degradation. Neurons are particularly dependent upon this "proteostasis" system, failures in which lead to neurodegenerative disease. In this review, we identify opportunities for modulating molecular chaperone activity with small molecules, which could lower the burden of misfolded protein within neurons, reducing cell death and ameliorating the effects of neurodegeneration. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

Publication types

  • Review

MeSH terms

  • Animals
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Neurodegenerative Diseases / metabolism*
  • Proteostasis

Substances

  • Heat-Shock Proteins