TY - JOUR
T1 - Modulating NRF2 in disease
T2 - Timing is everything
AU - Dodson, Matthew
AU - De La Vega, Montserrat Rojo
AU - Cholanians, Aram B.
AU - Schmidlin, Cody J.
AU - Chapman, Eli
AU - Zhang, Donna D.
N1 - Funding Information:
The authors are funded by the following grants from the National Institutes of Health: ES026845 (D.D.Z.), DK109555 (D.D.Z.), ES023758 (E.C., D.D.Z.), ES004940 (D.D.Z.), and ES006694 (a center grant).
Publisher Copyright:
© 2019 by Annual Reviews. All rights reserved.
PY - 2019/1/6
Y1 - 2019/1/6
N2 - 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.
AB - 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.
KW - Cancer
KW - Clinical trials
KW - Disease
KW - KEAP1
KW - NRF2
KW - Therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85059795824&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059795824&partnerID=8YFLogxK
U2 - 10.1146/annurev-pharmtox-010818-021856
DO - 10.1146/annurev-pharmtox-010818-021856
M3 - Review article
C2 - 30256716
AN - SCOPUS:85059795824
SN - 0362-1642
VL - 59
SP - 555
EP - 575
JO - Annual review of pharmacology and toxicology
JF - Annual review of pharmacology and toxicology
ER -