Modulating NRF2 in Disease: Timing Is Everything

The transcription factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) is a central regulator of redox, metabolic, and protein homeostasis that intersects with many other signaling cascades. Although the understanding of the complex nature of NRF2 signaling continues to grow, there is o...

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Published inAnnual review of pharmacology and toxicology Vol. 59; no. 1; pp. 555 - 575
Main Authors Dodson, Matthew, de la Vega, Montserrat Rojo, Cholanians, Aram B, Schmidlin, Cody J, Chapman, Eli, Zhang, Donna D
Format Journal Article
LanguageEnglish
Published United States Annual Reviews 06.01.2019
Subjects
Animals
cancer
clinical trials
disease
Humans
KEAP1
NF-E2-Related Factor 2 - metabolism
NRF2
Signal Transduction - physiology
therapeutics
KEAP1
therapeutics
cancer
clinical trials
disease
NRF2
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Summary:The transcription factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) is a central regulator of redox, metabolic, and protein homeostasis that intersects with many other signaling cascades. Although the understanding of the complex nature of NRF2 signaling continues to grow, there is only one therapeutic targeting NRF2 for clinical use, dimethyl fumarate, used for the treatment of multiple sclerosis. The discovery of new therapies is confounded by the fact that NRF2 levels vary significantly depending on physiological and pathological context. Thus, properly timed and targeted manipulation of the NRF2 pathway is critical in creating effective therapeutic regimens. In this review, we summarize the regulation and downstream targets of NRF2. Furthermore, we discuss the role of NRF2 in cancer, neurodegeneration, and diabetes as well as cardiovascular, kidney, and liver disease, with a special emphasis on NRF2-based therapeutics, including those that have made it into clinical trials.
ISSN:0362-1642
1545-4304
DOI:10.1146/annurev-pharmtox-010818-021856