Inhibiting BTB domain and CNC homolog 1 (Bach1) as an alternative to increase Nrf2 activation in chronic diseases

Biochim Biophys Acta Gen Subj. 2022 Jun;1866(6):130129. doi: 10.1016/j.bbagen.2022.130129. Epub 2022 Mar 12.

Abstract

BTB and CNC homology 1 (Bach1) is a protein that forms nuclear heterodimers with the small musculoaponeurotic fibrosarcoma (sMaf). These bind to genomic DNA, promoting the inhibition of the synthesis of a range of antioxidant enzymes. This heterodimer antagonises the actions of nuclear factor erythroid 2-related factor-2 (Nrf2), a master regulator of cytoprotective responses in the cells. Studies have shown that Nrf2 expression is downregulated and Bach1 expression upregulated in many chronic diseases; hence Nrf2 activators and Bach1 inhibitors need to be investigated for their potential to mitigate inflammation and improve antioxidant responses in the chronic burden of lifestyle diseases, including chronic kidney disease. Thus, this review will discuss the status of Bach1 in such diseases and the use of possible inhibitors as a promising therapeutic approach.

Keywords: Bach1; Chronic kidney disease; Inflammation; Nrf2; Oxidative stress.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants
  • BTB-POZ Domain*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Chronic Disease
  • Humans
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Signal Transduction

Substances

  • Antioxidants
  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • NF-E2-Related Factor 2