Transcription factor NRF2 as a promising therapeutic target for Alzheimer's disease

Free Radic Biol Med. 2020 Nov 1:159:87-102. doi: 10.1016/j.freeradbiomed.2020.06.028. Epub 2020 Jul 28.

Abstract

Oxidative stress is considered as one of the pathogenesis of Alzheimer's disease (AD) and plays an important role in the occurrence and development of AD. Nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulatory of oxidative stress defence. There is growing evidence indicating the relationship between NRF2 and AD. NRF2 activation mitigates multiple pathogenic processes involved in AD by upregulating antioxidative defense, inhibiting neuroinflammation, improving mitochondrial function, maintaining proteostasis, and inhibiting ferroptosis. In addition, several NRF2 activators are currently being evaluated as AD therapeutic agents in clinical trials. Thus, targeting NRF2 has been the focus of a new strategy for prevention and treatment of AD. In this review, the role of NRF2 in AD and the NRF2 activators advanced into clinical and preclinical studies will be summarized.

Keywords: Alzheimer’s disease; Ferroptosis; NRF2; Neuroinflammation; Oxidative stress; Proteostasis.

Publication types

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

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / genetics
  • Antioxidants / therapeutic use
  • Gene Expression Regulation
  • Humans
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress

Substances

  • Antioxidants
  • NF-E2-Related Factor 2