ReviewMolecular neurobiology2025
The KEAP1-Cullin3-RBX1-Nrf2 Axis in Redox Homeostasis: Molecular Mechanisms, Pathophysiological Roles, and Precision Therapeutic Opportunities.
Review in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- Design and Synthesis of Morroniside Derivatives Targeting HChemMedChem · 2026Article
- Nrf2 Activators in Parkinson's Disease: Modulating Mitophagy and Regulating Cuproptosis.Molecular neurobiology · 2026Review
- Polydatin Attenuates Sepsis-Induced Lung Injury by Inhibiting Neutrophil Extracellular Traps Formation via Nrf2/HO-1 Pathway.Biomedicines · 2026Article
- Epigenetic Mechanisms Regulating Ferroptosis in Ischemic Stroke: From Pathogenesis to Therapeutic Targets.Cellular and molecular neurobiology · 2026Review
- Esculentoside A mitigates oxidative stress and neuronal apoptosis in spinal cord injury by modulating the Nrf2/HO-1 pathway.Frontiers in neurology · 2026Article
- Intersections between proteostasis and immunity: insights from Caenorhabditis elegans.Disease models & mechanisms · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The KEAP1-Cullin3-RBX1 E3 ubiquitin ligase complex functions as the central molecular gatekeeper of cellular redox homeostasis by tightly regulating the degradation of nuclear factor erythroid 2-related factor 2, a master transcriptional regulator of antioxidant and cytoprotective genes. Under basal physiological conditions, this complex ensures a finely tuned, transient activation of Nrf2, thereby preventing unnecessary antioxidant gene expression while maintaining readiness against oxidative insults. In response to oxidative or electrophilic stress, conformational modifications in KEAP1 cysteine residues impair Nrf2 ubiquitination, enabling its nuclear translocation and activation of a wide range of target genes involved in detoxification, metabolic regulation, and cellular repair. While transient activation of Nrf2 is protective against acute stress and chronic degenerative disorders, persistent activation-often due to mutations in KEAP1 or NFE2L2-can drive tumorigenesis, chemoresistance, metabolic reprogramming, and immune evasion. This review summarizes the structural and mechanistic underpinnings of the KEAP1-Cullin3-RBX1 complex, explores the dual context-dependent roles of Nrf2 in health and disease, and highlights current therapeutic strategies aimed at modulating this pathway. However, despite significant advances, limitations remain in fully elucidating the context-specific consequences of Nrf2 activation, the heterogeneity of its downstream effects across cancer types, and the long-term safety of pharmacological Nrf2 modulators. Further research is therefore essential to define biomarkers of Nrf2 dependency, optimize therapeutic windows, and integrate pathway modulation into precision medicine frameworks. A deeper understanding of this regulatory axis may ultimately transform Nrf2 from a compelling molecular target into a cornerstone of redox-based precision therapeutics.
Indexed as
Identifiers
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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 Socratic graph.