NRF2-targeted therapeutics: New targets and modes of NRF2 regulation

Montserrat Rojo de la Vega, Matthew Dodson, Eli Chapman, Donna Zhang

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

Pharmacological activation of the transcription factor nuclear factor-erythroid derived 2-like 2 (NRF2), the key regulator of the cellular antioxidant response, has been recognized as a feasible strategy to reduce oxidative/electrophilic stress and prevent carcinogenesis or other chronic illnesses, such as diabetes and chronic kidney disease. In contrast, due to the discovery of the “dark side” of NRF2, where prolonged activation of NRF2 causes tissue damage, cancer progression, or chemoresistance, efforts have been devoted to identify inhibitors. Currently, only one NRF2 activator has been approved for use in the clinic, while no specific NRF2 inhibitors have been discovered. Future development of NRF2-targeted therapeutics should be based on our current understanding of the regulatory mechanisms of this protein. In addition to the KEAP1-dependent mechanisms, the recent discovery of other pathways involved in the degradation of NRF2 have opened up new possibilities for the development of safe and specific therapeutics. Here, we review available and putative NRF2-targeted therapeutics and discuss their modes of action as well as their potential for disease prevention and treatment.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
JournalCurrent Opinion in Toxicology
Volume1
DOIs
StatePublished - 2016

Fingerprint

Erythroid-Specific DNA-Binding Factors
Chemical activation
Oxidative stress
NF-E2 Transcription Factor
Medical problems
Transcription Factors
Antioxidants
Tissue
Chronic Renal Insufficiency
Degradation
Carcinogenesis
Oxidative Stress
Chronic Disease
Therapeutics
Pharmacology
Proteins
Neoplasms

Keywords

  • Autophagy
  • Cancer
  • Chemoprevention
  • Diabetes
  • Electrophiles
  • NRF2

ASJC Scopus subject areas

  • Toxicology

Cite this

NRF2-targeted therapeutics : New targets and modes of NRF2 regulation. / Rojo de la Vega, Montserrat; Dodson, Matthew; Chapman, Eli; Zhang, Donna.

In: Current Opinion in Toxicology, Vol. 1, 2016, p. 62-70.

Research output: Contribution to journalReview article

@article{52998ab0438649729531510c5077b77f,
title = "NRF2-targeted therapeutics: New targets and modes of NRF2 regulation",
abstract = "Pharmacological activation of the transcription factor nuclear factor-erythroid derived 2-like 2 (NRF2), the key regulator of the cellular antioxidant response, has been recognized as a feasible strategy to reduce oxidative/electrophilic stress and prevent carcinogenesis or other chronic illnesses, such as diabetes and chronic kidney disease. In contrast, due to the discovery of the “dark side” of NRF2, where prolonged activation of NRF2 causes tissue damage, cancer progression, or chemoresistance, efforts have been devoted to identify inhibitors. Currently, only one NRF2 activator has been approved for use in the clinic, while no specific NRF2 inhibitors have been discovered. Future development of NRF2-targeted therapeutics should be based on our current understanding of the regulatory mechanisms of this protein. In addition to the KEAP1-dependent mechanisms, the recent discovery of other pathways involved in the degradation of NRF2 have opened up new possibilities for the development of safe and specific therapeutics. Here, we review available and putative NRF2-targeted therapeutics and discuss their modes of action as well as their potential for disease prevention and treatment.",
keywords = "Autophagy, Cancer, Chemoprevention, Diabetes, Electrophiles, NRF2",
author = "{Rojo de la Vega}, Montserrat and Matthew Dodson and Eli Chapman and Donna Zhang",
year = "2016",
doi = "10.1016/j.cotox.2016.10.005",
language = "English (US)",
volume = "1",
pages = "62--70",
journal = "Current Opinion in Toxicology",
issn = "2468-2020",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - NRF2-targeted therapeutics

T2 - New targets and modes of NRF2 regulation

AU - Rojo de la Vega, Montserrat

AU - Dodson, Matthew

AU - Chapman, Eli

AU - Zhang, Donna

PY - 2016

Y1 - 2016

N2 - Pharmacological activation of the transcription factor nuclear factor-erythroid derived 2-like 2 (NRF2), the key regulator of the cellular antioxidant response, has been recognized as a feasible strategy to reduce oxidative/electrophilic stress and prevent carcinogenesis or other chronic illnesses, such as diabetes and chronic kidney disease. In contrast, due to the discovery of the “dark side” of NRF2, where prolonged activation of NRF2 causes tissue damage, cancer progression, or chemoresistance, efforts have been devoted to identify inhibitors. Currently, only one NRF2 activator has been approved for use in the clinic, while no specific NRF2 inhibitors have been discovered. Future development of NRF2-targeted therapeutics should be based on our current understanding of the regulatory mechanisms of this protein. In addition to the KEAP1-dependent mechanisms, the recent discovery of other pathways involved in the degradation of NRF2 have opened up new possibilities for the development of safe and specific therapeutics. Here, we review available and putative NRF2-targeted therapeutics and discuss their modes of action as well as their potential for disease prevention and treatment.

AB - Pharmacological activation of the transcription factor nuclear factor-erythroid derived 2-like 2 (NRF2), the key regulator of the cellular antioxidant response, has been recognized as a feasible strategy to reduce oxidative/electrophilic stress and prevent carcinogenesis or other chronic illnesses, such as diabetes and chronic kidney disease. In contrast, due to the discovery of the “dark side” of NRF2, where prolonged activation of NRF2 causes tissue damage, cancer progression, or chemoresistance, efforts have been devoted to identify inhibitors. Currently, only one NRF2 activator has been approved for use in the clinic, while no specific NRF2 inhibitors have been discovered. Future development of NRF2-targeted therapeutics should be based on our current understanding of the regulatory mechanisms of this protein. In addition to the KEAP1-dependent mechanisms, the recent discovery of other pathways involved in the degradation of NRF2 have opened up new possibilities for the development of safe and specific therapeutics. Here, we review available and putative NRF2-targeted therapeutics and discuss their modes of action as well as their potential for disease prevention and treatment.

KW - Autophagy

KW - Cancer

KW - Chemoprevention

KW - Diabetes

KW - Electrophiles

KW - NRF2

UR - http://www.scopus.com/inward/record.url?scp=85016785956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016785956&partnerID=8YFLogxK

U2 - 10.1016/j.cotox.2016.10.005

DO - 10.1016/j.cotox.2016.10.005

M3 - Review article

AN - SCOPUS:85016785956

VL - 1

SP - 62

EP - 70

JO - Current Opinion in Toxicology

JF - Current Opinion in Toxicology

SN - 2468-2020

ER -