The Keap1-Nrf2 pathway: From mechanism to medical applications

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

The Keap1-Nrf2 pathway is the body’s primary inducible response to oxidative stress. Since the discovery in 1997 that Nrf2 is responsible for the expression of cytoprotective genes, an intricate molecular mechanism has been revealed through which the stress sensor protein Keap1 tightly regulates Nrf2 activity. In the nonstressed state, Keap1 promotes the ubiquitin-dependent degradation of Nrf2, while in response to oxidative or electrophilic stress, Keap1‘s ubiquitin ligase activity is inactivated, allowing Nrf2 to escape degradation and activate its antioxidant and anti-inflammatory transcription programs. Recent advances have revealed that in addition to oxidative stress, dysfunctional autophagy, endogenous primary metabolism metabolites, and immune metabolites are also able to regulate Nrf2‘s activity. This integration of Nrf2 activity into multiple cellular pathways highlights its importance for cellular survival and homeostasis and suggests that the pharmacological modulation of Nrf2 activity can provide beneficial effects in a number of diverse disease contexts.

Original languageEnglish
Title of host publicationOxidative Stress
Subtitle of host publicationEustress and Distress
PublisherElsevier
Pages125-147
Number of pages23
ISBN (Electronic)9780128186060
DOIs
Publication statusPublished - 2019 Jan 1

Keywords

  • Antioxidants
  • Keap1
  • Nrf2
  • Oxidative stress response
  • Reactive cysteine residues
  • Stress sensor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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