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FDA\u2010approved Nrf2 activators, Tecfidera and Skyclarys for patients with multiple sclerosis and Friedreich's ataxia, respectively, are non\u2010specific alkylating agents exerting side effects. Nrf2 is under feedback regulation through its target gene, transcriptional repressor Bach1. Specifically, in Parkinson's disease and other neurodegenerative diseases with Bach1 dysregulation, excessive Bach1 accumulation interferes with Nrf2 activation. Bach1 is a heme sensor protein, which, upon heme binding, is targeted for proteasomal degradation, relieving the repression of Nrf2 target genes. Ideally, a combination of Nrf2 stabilization and Bach1 inhibition is necessary to achieve the full therapeutic benefits of Nrf2 activation. Here, we discuss recent advances and future perspectives in developing small molecule inhibitors of Bach1, highlighting the significance of the Bach1\/Nrf2 signaling pathway as a promising neurotherapeutic strategy.<\/jats:p>","DOI":"10.1002\/bies.202300176","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T04:44:19Z","timestamp":1698986659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Emerging small molecule inhibitors of Bach1 as therapeutic agents: Rationale, recent advances, and future perspectives"],"prefix":"10.1002","volume":"46","author":[{"given":"Dmitry M.","family":"Hushpulian","sequence":"first","affiliation":[{"name":"Faculty of Biology and Biotechnologies Higher School of Economics  Moscow Russia"},{"name":"A.N. 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