NRF2 as a Therapeutic Target in Neurodegenerative Diseases

ASN Neuro. 2020 Jan-Dec:12:1759091419899782. doi: 10.1177/1759091419899782.

Abstract

Increased reactive oxygen species production and oxidative stress have been implicated in the pathogenesis of numerous neurodegenerative conditions including among others Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Friedrich’s ataxia, multiple sclerosis, and stroke. The endogenous antioxidant response pathway protects cells from oxidative stress by increasing the expression of cytoprotective enzymes and is regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). In addition to regulating the expression of antioxidant genes, NRF2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. This is because mitochondrial dysfunction and neuroinflammation are features of many neurodegenerative diseases as well NRF2 has emerged as a promising therapeutic target. Here, we review evidence for a beneficial role of NRF2 in neurodegenerative conditions and the potential of specific NRF2 activators as therapeutic agents.

Keywords: bioenergetics; dementia and neurological disorders; neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / metabolism
  • Antioxidants / administration & dosage
  • Antioxidants / metabolism
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Humans
  • NF-E2-Related Factor 2 / antagonists & inhibitors
  • NF-E2-Related Factor 2 / metabolism*
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species