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NeurodegenerativeTherapeutics

Nrf2/Bach1 signaling axis: A promising multifaceted therapeutic strategy for neurodegenerative diseases

Neurotherapeutics

Abstract

The NRF2/BACH1 signaling axis is a promising therapeutic target. BACH1 is a transcriptional repressor that antagonizes NRF2. Non-electrophilic small molecules like HPPE simultaneously activate NRF2 and inhibit BACH1.

Key Findings

  • BACH1 is key transcriptional repressor of NRF2 target genes
  • BACH1 inhibition provides more specific NRF2 activation
  • Non-electrophilic HPPE simultaneously activates NRF2 and inhibits BACH1
  • Avoids off-target effects of electrophilic NRF2 activators

Clinical Significance

Identifies BACH1 inhibition as next-generation approach to NRF2 activation with superior specificity.

Citation

Nrf2/Bach1 axis for neurodegenerative diseases. (2025). Neurotherapeutics.

DOI: 10.1016/j.neurot.2025.e00064