NRF2 as a Therapeutic Target in Neurodegenerative Diseases

• Published in: ASN neuro Vol. 12; no. 1; p. 1759091419899782
• Main Authors: Brandes, Mikah S., Gray, Nora E.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2020; Sage Publications Ltd; Taylor & Francis
• Subjects: Alzheimer's disease; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - metabolism; Antioxidants; Antioxidants - administration & dosage; Antioxidants - metabolism; Ataxia; Dementia; Disease; Drug Delivery Systems - methods; Drug Delivery Systems - trends; Humans; Huntingtons disease; Inflammation; Mitochondria; Movement disorders; Multiple sclerosis; Neurodegenerative diseases; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - metabolism; NF-E2-Related Factor 2 - antagonists & inhibitors; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Parkinson's disease; Reactive oxygen species; Reactive Oxygen Species - metabolism; Review; Therapeutic applications; bioenergetics; neurodegenerative diseases; dementia and neurological disorders
• ISSN: 1759-0914; 1759-0914
• DOI: 10.1177/1759091419899782

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.