ReviewFrontiers in aging neuroscience2021
Challenges and Limitations of Targeting the Keap1-Nrf2 Pathway for Neurotherapeutics: Bach1 De-Repression to the Rescue.
Review in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Restoring autophagy-apoptosis balance in diabetic cardiomyopathy via a biomimetic, ROS-responsive nanocarrier associated with Mst1 pathway modulation.Journal of nanobiotechnology · 2026Article
- The Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Crosstalk Between Oxidative Stress and M1/M2 Microglial Polarization Following Ischemic Stroke.Molecular neurobiology · 2026Review
- Bioinspired lipid droplets nanoplatform for periodontitis therapy: Integrated antibacterial, mitochondrial repair, and immunomodulatory functions.Materials today. Bio · 2026Article
- Intersection of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Investigation of the Protective Effects of Aripiprazole on Methylphenidate-induced Neurotoxicity in Rats.Molecular neurobiology · 2025Article
- Nrf2/Bach1 signaling axis: A promising multifaceted therapeutic strategy for Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Role of NRF2 in Pathogenesis of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Glutathione dynamics in subcellular compartments and implications for drug development.Current opinion in chemical biology · 2024Review
- Pseudolaric acid B exerts an antifungal effect and targets SIRT1 to ameliorate inflammation by regulating Nrf2/NF-κB pathways in fungal keratitis.Inflammopharmacology · 2024Article
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Emerging small molecule inhibitors of Bach1 as therapeutic agents: Rationale, recent advances, and future perspectives.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- Targeting the NRF2 pathway for disease modification in neurodegenerative diseases: mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway.Journal of Zhejiang University. Science. B · 2023Review
- Review
- Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Normal and Pathological NRF2 Signalling in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2022Review
- Activation of the Nrf2 Pathway as a Therapeutic Strategy for ALS Treatment.Molecules (Basel, Switzerland) · 2022Review
- The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- Bach1 derepression is neuroprotective in a mouse model of Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
The Keap1-Nrf2 signaling axis is a validated and promising target for cellular defense and survival pathways. This minireview discusses the potential off-target effects and their impact on future drug development originating from Keap1-targeting small molecules that function as displacement activators of the redox-sensitive transcription factor Nrf2. We argue that small-molecule displacement activators, similarly to electrophiles, will release both Nrf2 and other Keap1 client proteins from the ubiquitin ligase complex. This non-specificity is likely unavoidable and may result in off-target effects during Nrf2 activation by targeting Keap1. The small molecule displacement activators may also target Kelch domains in proteins other than Keap1, causing additional off-target effects unless designed to ensure specificity for the Kelch domain only in Keap1. A potentially promising and alternative therapeutic approach to overcome this non-specificity emerging from targeting Keap1 is to inhibit the Nrf2 repressor Bach1 for constitutive activation of the Nrf2 pathway and bypass the Keap1-Nrf2 complex.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.