Modulating NRF2 in disease: Timing is everything

Matthew Dodson, Montserrat Rojo De La Vega, Aram B. Cholanians, Cody J. Schmidlin, Eli Chapman, Donna Zhang

Research output: Contribution to journalReview article

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)555-575
Number of pages21
JournalAnnual Review of Pharmacology and Toxicology
Volume59
DOIs
StatePublished - Jan 6 2019

Keywords

  • Cancer
  • Clinical trials
  • Disease
  • KEAP1
  • NRF2
  • Therapeutics

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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