ReviewRedox biology2022
Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway.
Review in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 2 of them syntheses that pooled it.
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
214 citing papers in PubMed, 2 syntheses or guidelines pooled it, 396 citations in OpenAlex.
- The Role of c-Abl in Alzheimer's Disease: Guilty or not Guilty?Cellular and molecular neurobiology · 2025Pooled it
- Combined Effect of Gamma Radiation and Heavy Metals on Some Living Organisms.Biological trace element research · 2025Pooled it
- Vitamin D3 Supplementation Modulates Inflammatory Protein CHI3L1/YKL-40 and Oxidative Stress Status in Multiple Sclerosis.Neuropsychopharmacology reports · 2025Trial
- Uric acid alleviates the inflammatory response in LPS-induced BV2 cells and MPTP-induced PD mice by resisting ferroptosis through the Nrf2 signalling pathway.Redox report : communications in free radical research · 2026Article
- Discovery of ferulic acid carbamate derivatives as dual-targeting agents of BuChE and Nrf2 for Alzheimer's disease.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Triptolide in renal disorders: dual roles of therapeutic potential and nephrotoxicity: a narrative review.Pharmaceutical biology · 2026Review
- A Subcellular Keap1-Nrf2 Disruption Strategy for Atopic Dermatitis Therapy.Journal of medicinal chemistry · 2026Article
- Effects ofInternational journal of molecular sciences · 2026Article
- Broccoli Sprout Extract Restores Renal Lipid Metabolism in High-Fat Diet-Fed Mice Involving Modulation of AMPK/Nrf2 Signaling and the NLRP3 Inflammasome.Food science & nutrition · 2026Article
- Targeted degradation of hepatic KEAP1 mitigates drug-induced liver injury via dual boosting NRF2 and PGAM5 signaling.Redox biology · 2026Article
- Hudi enteric-coated capsule and its active constituent polydatin suppress Th1/Th17-mediated intestinal inflammation by modulating the KEAP1-NFE2L2 signaling pathway.Precision clinical medicine · 2026Article
- Allosteric activation of Trx1 by antagonizing nitrative modification at tyrosine 49 confers neuroprotection against ischemic stroke.Redox biology · 2026Article
- Potential Involvement of Redox and Inflammatory Signalling in the Antihyperglycemic and Antioxidant Effects of Harmaline in Male Mice With Type 2 Diabetes.Endocrinology, diabetes & metabolism · 2026Article
- Dietary Antioxidants and Nrf2-Related Redox Responses in Sheep: Evidence, Limitations, and Implications for Health and Productivity.Veterinary sciences · 2026Review
- Pharmacological Mechanisms of Active Constituents from Traditional Chinese Medicine for Vitiligo Treatment.Pharmaceuticals (Basel, Switzerland) · 2026Review
- An Inulin-Type Atractylodes Macrocephala Polysaccharide Alleviates Weightlessness-Induced Bone Loss in Association with the Nrf2/HO-1 Pathway.Nutrients · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Arctigenin discovered by high-throughput screening ameliorates doxorubicin-induced cardiotoxicity as a novel natural KEAP1-NRF2 inhibitor.Journal of pharmaceutical analysis · 2026Article
- Targeting of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Signaling Pathway in Age-Related Eye Diseases: Molecular Mechanisms and Opportunities for therapy.Journal of biochemical and molecular toxicology · 2026Review
- TrxR Inhibition and Nrf2-FOXO3 Modulation by Repurposed Drugs: A Redox Strategy to Reverse Cancer Multidrug Resistance.Drug development research · 2026Review
154 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The KEAP1-NRF2-ARE signaling pathway plays a central role in mediating the adaptive cellular stress response to oxidative and electrophilic chemicals. This canonical pathway has been extensively studied and reviewed in the past two decades, but rarely was it looked at from a quantitative signaling perspective. Signal amplification, i.e., ultrasensitivity, is crucially important for robust induction of antioxidant genes to appropriate levels that can adequately counteract the stresses. In this review article, we examined a number of well-known molecular events in the KEAP1-NRF2-ARE pathway from a quantitative perspective with a focus on how signal amplification can be achieved. We illustrated, by using a series of mathematical models, that redox-regulated protein sequestration, stabilization, translation, nuclear trafficking, DNA promoter binding, and transcriptional induction - which are embedded in the molecular network comprising KEAP1, NRF2, sMaf, p62, and BACH1 - may generate highly ultrasensitive NRF2 activation and antioxidant gene induction. The emergence and degree of ultrasensitivity depend on the strengths of protein-protein and protein-DNA interaction and protein abundances. A unique, quantitative understanding of signal amplification in the KEAP1-NRF2-ARE pathway will help to identify sensitive targets for the prevention and therapeutics of oxidative stress-related diseases and develop quantitative adverse outcome pathway models to facilitate the health risk assessment of oxidative chemicals.
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Identifiers
What OpenQuestion holds
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.