Chemopreventive promise of targeting the Nrf2 pathway

Melinda S. Yates, Thomas W Kensler

Research output: Contribution to journalArticle

Abstract

The Kelch ECH associating protein 1-nuclear factor-E2-related factor 2-antioxidant response element (Keap 1-Nrf2-ARE) signaling pathway regulates several protective mechanisms including expression of conjugating and antioxidative genes, antiinflammatory responses, the molecular chaperone/stress response system and the ubiquitin/proteasome system. The Nrf2-mediated response alters susceptibility to carcinogenesis, acute chemical toxicity, oxidative stress, asthma, acute inflammation, septic shock and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Studies using natural and synthetic chemical inducers that activate Nrf2 signaling have demonstrated protective efficacy in many animal models of disease. Conversely, studies in Nrf2-disrupted mice indicate they exhibit increased sensitivity to many of these diseases. Thus, activation of Keap1-Nrf2-ARE signaling constitutes a broad protective response, making Nrf2 and its interacting partners important targets for chemoprevention. However, additional studies are needed to characterize Keap1-Nrf2-ARE signaling in humans to further develop exceptionally potent activators of the pathway and further understand the potential consequences of altering this system.

Original languageEnglish (US)
Pages (from-to)109-117
Number of pages9
JournalDrug News and Perspectives
Volume20
Issue number2
DOIs
StatePublished - Mar 2007

Fingerprint

NF-E2-Related Factor 2
Antioxidant Response Elements
Animal Disease Models
Molecular Chaperones
Chemoprevention
Proteasome Endopeptidase Complex
Septic Shock
Ubiquitin
Neurodegenerative Diseases
Parkinson Disease
Alzheimer Disease
Carcinogenesis
Oxidative Stress
Anti-Inflammatory Agents
Asthma
Inflammation
Genes
Proteins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Chemopreventive promise of targeting the Nrf2 pathway. / Yates, Melinda S.; Kensler, Thomas W.

In: Drug News and Perspectives, Vol. 20, No. 2, 03.2007, p. 109-117.

Research output: Contribution to journalArticle

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