Cited by 997Genomics, phytochemicals, and oxidative stressRedox biology and oxidative stressGlutathione Transferases and Polymorphisms

The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.

Molecular basis of the Keap1–Nrf2 system

Open access

Suzuki, Takafumi, Yamamoto, Masayuki·2015·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2015.06.006

Open this paper in CoChat — free account

Abstract

Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes, and Keap1 (Kelch-like ECH-associated protein 1), an adaptor subunit of Cullin 3-based E3 ubiquitin ligase, regulates Nrf2 activity. Keap1 also acts as a sensor for oxidative and electrophilic stresses. Keap1 retains multiple sensor cysteine residues that detect various stress stimuli. Increasing attention has been paid to the roles that Nrf2 plays in the protection of our bodies against drug toxicity and stress-induced diseases. On the other hand, Nrf2 is found to promote both oncogenesis and cancer cell resistance against chemotherapeutic drugs. Thus, although Nrf2 acts to protect our body from deleterious stresses, cancer cells hijack the Nrf2 activity to support their malignant growth. Nrf2 has emerged as a new therapeutic target, and both inducers and inhibitors of Nrf2 are awaited. Studies challenging the molecular basis of the Keap1-Nrf2 system functions are now critically important to improve translational studies of the system. Indeed, recent studies identified cross talk between Nrf2 and other signaling pathways, which provides new insights into the mechanisms by which the Keap1-Nrf2 system serves as a potent regulator of our health and disease.

Integrity signals

Registry

Crossref · 10.1016/j.freeradbiomed.2015.06.006

Cites

84 of 84 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634
Self-citation
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
Komatsu, M., Kurokawa, H., Waguri, S., Taguchi, K., Kobayashi, A., Ichimura, Y., Sou, Y.-S., Ueno, I., Sakamoto, A., Tong, K. I., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2021 · Cited by 2,288
Self-citation
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277
Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,210
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947
Self-citation
Nrf2–Keap1 defines a physiologically important stress response mechanism
Motohashi, H., & Yamamoto, M. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.003 · Cited by 1,725
Self-citation
Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480
Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., & Motohashi, H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.016 · Cited by 1,395
Self-citation

Show all 84 references

Sorted by citations

Items 701–800 of 997

Identification of novel Nrf2/Keap1 pathway mutations in pediatric acute lymphoblastic leukemia
Akın, D. F., Aktaş, S. H., Ünal, M. A., & Kankılıç, T. (2019) · Pediatric Hematology and Oncology · doi:10.1080/08880018.2019.1682090 · Cited by 9
Nuclear factor erythroid 2-related factor 2 potentiates the generation of inflammatory cytokines by intestinal epithelial cells during hyperoxia by inducing the expression of interleukin 17D
Liu, X., Li, T., Liu, Y., Sun, S., & Liu, D. (2021) · Toxicology · doi:10.1016/j.tox.2021.152820 · Cited by 9
Screening a redox library identifies the anti-tumor drug Hinokitiol for treating intrahepatic cholangiocarcinoma
Bai, P., Chen, G., Yang, H., Chen, H., Wan, L., Zhang, Y., Zhang, B., Zeng, Q., Fan, Z., Pei, X., et al. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2701018 · Cited by 9
Loss of serine/threonine protein kinase 25 in retinal ganglion cells ameliorates high glucose-elicited damage through regulation of the AKT-GSK-3β/Nrf2 pathway
Zhou, Z., Li, H., Bai, S., Xu, Z., & Jiao, Y. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.02.044 · Cited by 9
LCZ696 Ameliorates Isoproterenol-Induced Acute Heart Failure in Rats by Activating the Nrf2 Signaling Pathway
Hou, M., Lu, L., Wu, X., & Liu, H. (2022) · Applied Bionics and Biomechanics · doi:10.1155/2022/6077429 · Cited by 9
Retracted
Astragaloside IV alleviates 1-deoxysphinganine-induced mitochondrial dysfunction during the progression of chronic kidney disease through p62-Nrf2 antioxidant pathway
Gui, T., Chen, Q., Li, J., Lu, K., Li, C., Xu, B., Chen, Y., Men, J., Kullak-Ublick, G. A., Wang, W., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1092475 · Cited by 11
Activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress
Xu, J., Wu, L., Zhang, Y., Gu, H., Huang, Z., Zhou, K., & Yin, X. (2017) · Oncotarget · doi:10.18632/oncotarget.22055 · Cited by 9
Quantitative Structure-Activity Relationship Model to Predict Antioxidant Effects of the Peptide Fraction Extracted from a Co-Culture System of Chlorella pyrenoidosa and Yarrowia lipolytica
Liu, H., Li, S., Zhong, Y., Liu, J., Liu, H., Cheng, J., Ma, L., Huang, Y., Cai, X., Liu, H., et al. (2019) · Marine Drugs · doi:10.3390/md17110633 · Cited by 9
ERK signaling licenses SKN-1A/NRF1 for proteasome production and proteasomal stress resistancePreprint
Zhang, P., Qu, H.-Y., Wu, Z., Na, H., Hourihan, J. M., Zhang, F., Zhu, F., Isik, M., Walhout, A. J. M., Feng, Y., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.04.425272 · Cited by 8
In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture
Aquino, A. M., Fioretto, M. N., Alonso-Costa, L. G., Rocha, V. A., de Souza, P. V., Magosso, N. S. S., Barbisan, L. F., Justulin, L. A., Flaws, J. A., & Scarano, W. R. (2024) · Environmental Toxicology · doi:10.1002/tox.24181 · Cited by 8
A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis
Li, H., Du, L., Li, J., Huang, Y., Lu, C., Deng, T., Yan, Y., Jin, Y., Wu, W., Gu, J., et al. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012712 · Cited by 8
Genistein as a renoprotective agent: mechanistic insights into antioxidant, anti-inflammatory, and fibrosis-regulating pathways
Kattna, A., & Singh, L. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10603-2 · Cited by 8
iKeap1 activates Nrf2 signaling to protect myocardial cells from oxygen glucose deprivation/re-oxygenation-induced oxidative injury
Jiang, Y., Gu, C., Xu, H., Shi, F., Zhang, X., & Wang, F. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.08.024 · Cited by 8
Tripartite motif-containing protein 16 protects against myocardial ischemia/reperfusion injury by affecting the Keap1/Nrf2 axis
Cui, Q., & Li, Y. (2021) · Cell and Tissue Research · doi:10.1007/s00441-021-03518-4 · Cited by 8
TPNA10168, an Nrf-2 activator, attenuates inflammatory responses independently of Nrf2 in microglial BV-2 cells: Involvement of the extracellular-signal-regulated kinase pathway
Izumi, Y., Tatsumoto, A., Horiuchi, N., Arifuku, M., Uegomori, M., Kume, T., & Kōyama, Y. (2022) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2022.02.004 · Cited by 8
Swinhoeic acid from Potentilla fragarioides ameliorates high glucose-induced oxidative stress and accumulation of ECM in mesangial cells via Keap1-dependent activation of Nrf2
Yao, H., Kong, M., Du, D., Ai, F., Li, J., & Li, Y. (2022) · Redox Report · doi:10.1080/13510002.2022.2134755 · Cited by 8
Lactobacillus plantarum fermented Laminaria japonica alleviates UVB-induced epidermal photoinflammation via the Keap-1/Nrf2 pathway
Song, Z., Sun, Q., Xu, Y., Tian, Y., Fang, J., Wang, Z., Geng, J., Wang, D., Wang, C., & Li, M. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105693 · Cited by 8
Mefenamic Acid-Upregulated Nrf2/SQSTM1 Protects Hepatocytes against Oxidative Stress-Induced Cell Damage
Lee, W., Mun, Y., Lee, K.-Y., Park, J., Chang, T., Choi, Y., & Lee, B. (2023) · Toxics · doi:10.3390/toxics11090735 · Cited by 9
WDR23 mediates NRF2 proteostasis and cytoprotective capacity in the hippocampus
Liu, J., Duangjan, C., Irwin, R. W., & Curran, S. P. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111914 · Cited by 8
Effect of Phenol and Alkylamide Interaction on α-Glucosidase Inhibition and Cellular Antioxidant Activity during In Vitro Digestion: Using Szechuan Pepper (Zanthoxylum genus) as a Model
Zhang, D., Lu, M., Liu, X., Wei, X., Lv, G., Shi, J., Battino, M. A., Chen, K., & Zou, X. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c01544 · Cited by 8
Erjingwan Extracts Exert Antiaging Effects of Skin through Activating Nrf2 and Inhibiting NF- κ B
Zhong, H., Hong, C., Han, Z., Hwang, S. J., Kim, B., Xu, Z., Lee, J., Kim, K. H., Jin, M. H., & Zou, C. (2019) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2019/5976749 · Cited by 9
Erythropoietin suppresses D-galactose-induced aging of rats via the PI3K/Akt/Nrf2-ARE pathway.
Wu, H., Chen, M., Yan, P., Yao, Q., Fan, J., Gao, Z., & Wang, H. (2018) · PubMed Central · Cited by 8
Carnosine Mitigates Biomarkers of Oxidative Stress, Improves Mitochondrial Function, and Alleviates Histopathological Alterations in the Renal Tissue of Cholestatic Rats
Farshad, O., Ommati, M. M., Yüzügülen, J., Jamshidzadeh, A., Mousavi, K., Ahmadi, Z., Azarpira, N., Ghaffari, H., Najibi, A., Shafaghat, M., et al. (2020) · Pharmaceutical Sciences · doi:10.34172/ps.2020.60 · Cited by 8
Guan Xin Dan Shen formulation protects db/db mice against diabetic cardiomyopathy via activation of Nrf2 signaling
Zhang, B., Zhang, C., Zhang, X., Sun, G., & Sun, X. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12170 · Cited by 8
Role of NRF2 cascade in determining the differential response of cervical cancer cells to anticancer drugs: an in vitro study
Ramesh, P. S., Raja, S., Udayakumar, S. H., Chandrashekar, S., Nataraj, S. M., & Devegowda, D. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06848-2 · Cited by 8
Natural product, bilobalide, improves joint health in rabbits with osteoarthritis by anti-matrix degradation and antioxidant activities
Ma, T., Chen, H., Ruan, H., Lv, L., Yu, Y., Jia, L., Zhao, J., Li, X., Zang, Y., Xu, X., et al. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.1034623 · Cited by 8
An Approach to Evaluate the Effective Cytoplasmic Concentration of Bioactive Agents Interacting with a Selected Intracellular Target Protein
Khramtsov, Y. V., Ulasov, A. V., Rosenkranz, A. A., Slastnikova, T. A., Lupanova, T. N., Georgiev, G. P., & Sobolev, A. S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020324 · Cited by 8
Senescence marker protein 30 confers neuroprotection in oxygen-glucose deprivation/reoxygenation-injured neurons through modulation of Keap1/Nrf2 signaling: Role of SMP30 in OGD/R-induced neuronal injury
Liu, W., Zhao, H., Su, Y., Wang, K., Li, J., Xue, S., Sun, X., & Qiu, Z. (2020) · Human & Experimental Toxicology · doi:10.1177/0960327120954243 · Cited by 8
Effects of dietary tributyrin supplementation in low fish meal diet containing high-Clostridium autoethanogenum protein on the growth performance, antioxidative capacity, lipid metabolism and intestinal microbiota of largemouth bass (Micropterus salmoides)
Luo, K., Shi, Y., Yang, K., Xu, Q., Jiang, Z., Gao, W., Wu, C., & Wang, Z. (2023) · Aquaculture Reports · doi:10.1016/j.aqrep.2023.101722 · Cited by 7
Selenium nanoparticles decorated with polysaccharides from Sargassum fusiforme protects against 6-OHDA-induced neurotoxicity in PC12 cells and rat model of Parkinson's disease
Zhao, H., Song, J., Wang, T., & Fan, X. (2024) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2024.102755 · Cited by 7
Activation of the NRF2 signaling pathway mitigates arthrofibrosis by suppressing myofibroblast ferroptosis through oxidative stress regulation
Zhu, S., Hou, J., Li, Y., Deng, W., Wang, Z., Qiao, M., Dai, Z., Huang, J., Jiang, L., Huang, J., et al. (2025) · Cell investigation. · doi:10.1016/j.clnves.2025.100020 · Cited by 7
Novel therapeutic approach in periodontitis: Sulforaphane attenuates disease progression via Nrf2-mediated antioxidant defense
Liu, Y., Li, T., Liao, Y.-L., Chen, J., Sheng, Y., Zhao, Y., He, Z., Tang, H., Wang, Y., Bian, Z., et al. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115002 · Cited by 7
Tussilagone attenuated cigarette smoke-induced chronic obstructive pulmonary disease through regulating Nrf2 and NF-κB/NLRP3 inflammasome via directly targeting cysteine 434 of KEAP1
Xu, L., Han, Q., Xu, Z.-P., Wang, X., Zhang, H., & Shen, T. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.07.019 · Cited by 7
Ozone rectal insufflation attenuates lung inflammation by inhibiting the TLR4/NF-κB pathway through upregulation of Nrf2 in mice with COPD-like pathology
Zhu, X., Zhao, Q., Wang, P., Cao, S., Williams, J. P., & An, J. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115676 · Cited by 8
Cartilage extracellular matrix regeneration with 10-gingerol via KEAP1-NRF2-ARE axis for osteoarthritis therapy
Ma, Y., Sun, C., Wang, Z., & Chen, C. (2025) · Archives of Pharmacal Research · doi:10.1007/s12272-025-01579-5 · Cited by 7
Recent Developments in Antioxidants from Natural Sources
Fuertes, P. O., & Corral, M. F. (2023) · Biochemistry · doi:10.5772/intechopen.104365 · Cited by 7
Sustained Nrf2 Overexpression-Induced Metabolic Deregulation Can Be Attenuated by Modulating Insulin/Insulin-like Growth Factor Signaling
Gumeni, S., Λάμπρου, Μ., Evangelakou, Z., Manola, M. S., & Trougakos, I. P. (2023) · Cells · doi:10.3390/cells12222650 · Cited by 8
A study on the function of methionine in growth, immunity, antioxidant, endoplasmic reticulum stress and apoptosis of largemouth bass (Micropterus salmoides)
Liang, H., Huang, D., Ren, M., Zhang, L., Mi, H., Aboseif, A. M., Xue, C., & Gu, J. (2024) · Aquaculture Reports · doi:10.1016/j.aqrep.2024.102531 · Cited by 7
Metabolically active and polyploid renal tissues rely on graded cytoprotection to drive developmental and homeostatic stress resilience
Burbridge, K., Holcombe, J., & Weavers, H. (2021) · Development · doi:10.1242/dev.197343 · Cited by 7
Novel cudraisoflavone J derivatives as potent neuroprotective agents for the treatment of Parkinson's disease via the activation of Nrf2/HO-1 signaling
Lu, Q., Gouda, N. A., Quan, G., Nada, H., Elkamhawy, A., Lee, D., Lee, C. H., Cho, J., & Lee, K. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114692 · Cited by 7
Isozyme-specific histone deacetylase 1/2 inhibitor K560 attenuates oxidative stress-induced retinal cell death
Tawarayama, H., Hirata, Y., Uchida, K., Himori, N., Uesato, S., & Nakazawa, T. (2022) · Neuroscience Letters · doi:10.1016/j.neulet.2022.136978 · Cited by 7
Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis
Tang, H., Liu, S., Yan, X., Jin, Y., He, X., Huang, H., Liu, L., Hu, W., & Wu, A. (2023) · Biology · doi:10.3390/biology12091208 · Cited by 7
7,8‑Dihydroxyflavone functions as an antioxidant through the inhibition of Kelch‑like ECH‑associated protein 1: Molecular docking and an in vivo approach in a rat model of ischemia‑reperfusion brain injury
Yueniwati, Y., Syaban, M. F. R., Kurniawan, D. B., Azam, A., Alvenia, D., Savira, Y. N., Muhammad, R. F., Adnani, B., Violita, A. H., Arviana, S. D., et al. (2024) · World Academy of Sciences Journal · doi:10.3892/wasj.2024.230 · Cited by 7
The short isoform of PML ‐ RAR α activates the NRF 2/ HO ‐1 pathway through a direct interaction with NRF 2
Li, Y., Wang, H., Wang, X. J., & Tang, X. (2017) · FEBS Letters · doi:10.1002/1873-3468.12779 · Cited by 7
Rooibos (Aspalathus linearis) and Honeybush (Cyclopiaspp.): From Bush Teas to Potential Therapy for Cardiovascular Disease
Windvogel, S. L. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.86410 · Cited by 7
Involvement of nuclear factor erythroid 2‑related factor�2 in�neonatal intestinal interleukin‑17D expression in hyperoxia
Liu, X., Zhang, D., Cai, Q., Liu, D., & Sun, S. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4697 · Cited by 7
Chemical genetics of regeneration: Contrasting temporal effects of CoCl2 on axolotl tail regeneration
Baddar, N. W. A. H., Dwaraka, V. B., Ponomareva, L. V., Thorson, J. S., & Voss, S. R. (2021) · Developmental Dynamics · doi:10.1002/dvdy.294 · Cited by 7
Exploration on the Mechanism of Ubiquitin Proteasome System in Cerebral Stroke
Li, Y., Wang, Y., & Zou, W. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.814463 · Cited by 7
Modulation of inflammatory mediators underlies the antitumor effect of the combination of morusin and docetaxel on prostate cancer cells
Fadil, S. A., Albadawi, D. A. I., Alshali, K. Z., Abdallah, H. M., & Saber, M. M. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117572 · Cited by 6
Medicinal Plant Survey: ‘Good for Humans, Good for Fishes!’
Steinberg, C. E. W. (2024) · Springer eBooks · doi:10.1007/978-3-031-70938-8_2 · Cited by 6
Hsa-miR-532-3p protects human decidual mesenchymal stem cells from oxidative stress in recurrent spontaneous abortion via targeting KEAP1
Zhou, H. H., Zhou, J., Liu, S., Niu, J., Pan, J., & Li, R. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103508 · Cited by 7
Sphaeropsidin A covalently binds to Cys 151 of Keap1 to attenuate LPS-induced acute pneumonia in mice
Yang, K., Han, Q., Xing, R.-X., Li, Z.-Y., Xu, L., Chen, L.-Z., Xiang, L., Ren, D., Hu, Q., Wang, X., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103621 · Cited by 6
Targeted activation of Nrf2 at sites of oxidative stress reverses doxorubicin-induced cognitive impairments in mice
Singh, A. K., Ruiz, D., Pandey, V. K., Rasheed, M. S. U., Turner, D. J. L., Avery, T. D., Abell, A. D., & Grace, P. M. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.06.037 · Cited by 7
Bardoxolone methyl inhibits ferroptosis through the Keap1‑Nrf2 pathway in renal tubular epithelial cells
Yoo, S., Kim, M., Bae, J., Lee, S. Y., & Koh, G. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13632 · Cited by 7
Modulating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in liver-brain axis disorders
Zhang, Y., & Zhang, Z. (2025) · World Journal of Psychiatry · doi:10.5498/wjp.v15.i9.108382 · Cited by 8
Redox Balance, Mitohormesis, and Organ Stress in Type 2 Diabetes Mellitus: Mechanistic Insights and the Therapeutic Role of SGLT2 Inhibitors
Otoda, T., Aihara, K., & Takayama, T. (2025) · Diabetology · doi:10.3390/diabetology6100111 · Cited by 7
Redefining cell death: ferroptosis as a game-changer in ophthalmology
Wei, Y., Lin, Y., Li, Y., Liu, J., Yang, Y., Chen, H., Han, Z., Wang, K., Tao, Q., Ju, Y., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1709354 · Cited by 8
Deciphering the cancer chemopreventive potential of phytochemicals: an integrative perspective on molecular targets and signaling networks
kaur, S., Ahmad, S. S., Raja, V., Mahajan, P., & Abdi, G. (2026) · Cancer Cell International · doi:10.1186/s12935-025-04109-x · Cited by 6
Neferine Pretreatment Attenuates Isoproterenol-Induced Cardiac Injury Through Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats
Sun, X., Gu, Y., Liu, X., Korla, P. K., & Hao, J. (2024) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-024-04917-3 · Cited by 6
DbGTi protein attenuates chromium (VI)-induced oxidative stress via activation of the Nrf2/HO-1 signalling pathway in zebrafish (Danio rerio) larval model
Jegadheeshwari, S., Santhi, J. J., Velayutham, M., Issac, P. K., & Kesavan, M. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.136099 · Cited by 6
Unveiling Smyd-2’s Role in Cytoplasmic Nrf-2 Sequestration and Ferroptosis Induction in Hippocampal Neurons After Cerebral Ischemia/Reperfusion
Liu, D., & Zhu, Y. Z. (2024) · Cells · doi:10.3390/cells13231969 · Cited by 6
Targeted proteome analysis with isotope-coded protein labels for monitoring the influence of dietary phytochemicals on the expression of cytoprotective proteins in primary human colon cells
Östreicher, C., Bartenbacher, S., & Pischetsrieder, M. (2017) · Journal of Proteomics · doi:10.1016/j.jprot.2017.06.023 · Cited by 6
Simulated microgravity promotes oxidative stress-induced apoptosis in ARPE-19 cells associated with Nrf2 signaling pathway
Huyan, T., Li, M., Chen, W., Zhou, X., Pei, D., Shang, P., & Wu, C. (2022) · Acta Astronautica · doi:10.1016/j.actaastro.2022.05.012 · Cited by 6
UHPLC-ESI-QE-Orbitrap-MS based metabolomics reveals the antioxidant mechanism of icaritin on mice with cerebral ischemic reperfusion
Tang, Y., Sun, L., Zhao, Y., Yao, J., Feng, Z., Liu, Z., Zhang, G., & Sun, C. (2023) · PeerJ · doi:10.7717/peerj.14483 · Cited by 6
Structural investigation of Keap1–Nrf2 protein–protein interaction (PPI) inhibitors for treating myocarditis through molecular simulations
Tuo, Y., Tang, Y., Yu, Y., Liang, H., Huang, B., Geng, S., & Wang, Y. (2023) · New Journal of Chemistry · doi:10.1039/d2nj03078k · Cited by 8
SIRT1-NRF2-TFEB axis-mediated hepatic lipophagy alleviates the lipid deposition induced by high glucose in yellow catfish Pelteobagrus fulvidraco
Wu, L., Tan, X.-Y., Xu, Y.-C., Zheng, H., Wei, X., Lv, W.-H., & Luo, Z. (2023) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2023.110894 · Cited by 6
Hepatoprotective effects of gentisic acid through its anti-oxidant properties in nicotinamide-streptozotocin induced diabetic mice.
Razliqi, R. N., Harooni, E., Neisi, N., Sameri, M. J., & Ahangarpour, A. (2023) · PubMed Central · doi:10.22038/ijbms.2023.70659.15359 · Cited by 6
Nuclear Factor Erythroid 2-Related Factor 2 as a Potential Therapeutic Target in Neonatal Hypoxic-Ischemic Encephalopathy
Liu, J., Zheng, D., Chen, L., Chen, S., & Min, J. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2305103 · Cited by 6
Antiaging and Neuroprotective Properties of Mediterranean Diet Components in Humans
Farooqui, A. A., & Farooqui, T. (2018) · Springer eBooks · doi:10.1007/978-981-13-1699-9_15 · Cited by 6
Methylmercury-induced hair cell loss requires hydrogen peroxide production and leukocytes in zebrafish embryos
Luo, Z., Guo, S., Ho, N. Y., Takamiya, M., Strähle, U., & Yang, L. (2021) · Toxicology Letters · doi:10.1016/j.toxlet.2021.12.012 · Cited by 6
Interplay of Cellular Nrf2/NF-κB Signalling after Plasma Stimulation of Malignant vs. Non-Malignant Dermal Cells
Manzhula, K., Rebl, A., Budde, K., & Rebl, H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252010967 · Cited by 6
Mangiferin promotes porcine oocyte maturation and delays the postovulatory aging process by up-regulating NRF2 levels
Yuan, X., Ji, H., Zhang, Y., Peng, H., Cao, N.-H., Ren, J.-J., Yao, X., Liang, X., Kim, N.-H., Xu, Y., et al. (2025) · Theriogenology · doi:10.1016/j.theriogenology.2025.117384 · Cited by 5
Effects of nitrite exposure on oxidative stress immune response and apoptosis in sea bass (Lateolabrax japonicus) during simulated live transport
Wang, J., Guo, M., Mei, J., & Xie, J. (2025) · Aquaculture International · doi:10.1007/s10499-025-02080-y · Cited by 5
The role of the NcRNA/ferroptosis axis in lung cancer: molecular mechanisms and potential therapeutic targets
Alimohammadi, M., Kahkesh, S., Cho, W. C. S., Farahani, N., Khoozani, M. F., Zare, A., Nejadheidari, A., Farani, M. R., Parizi, A. K., Asgharzadeh, F., et al. (2025) · APOPTOSIS · doi:10.1007/s10495-025-02127-8 · Cited by 5
Evaluation of polyethylene microplastics toxicity using Nrf2/ARE and MAPK/Nrf2 signaling pathways
Mohamed, M. M. A., Yousri, N. A., Khamis, N. H., Hakim, S. A. B. A., Elsayed, S. H., & Ali, E. A. E. (2025) · Toxicology Mechanisms and Methods · doi:10.1080/15376516.2025.2527154 · Cited by 5
TPNA10168, an Nrf2 activator, attenuates LPS-induced inflammation in microglia through modulation of MAPK and NF-κB pathways
Izumi, Y., Koide, E., Kobayashi, F., Ikawa, S., Takayama, M., Yamaki, K., Takeda, N., Yamada, T., Ueda, M., Kume, T., et al. (2025) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2025.07.001 · Cited by 5
Inhibition of Nrf2 Activity in Mitigating Cadmium-Induced Mitochondrial Damage and Pyroptosis
Xu, H., Yang, H. J., Ye, R., Cao, M., Li, S., Liu, C., & Li, L. (2025) · Biological Trace Element Research · doi:10.1007/s12011-025-04775-y · Cited by 5
Rosiglitazone Ameliorates Adverse Effects of High-Fat Diet in Largemouth Bass (Micropterus salmoides): Modulation of Lipid Metabolism, Antioxidant Capacity, Inflammatory Response, and Gut Microbiota
Yan, Y., Tang, Y., Chen, X., Chen, X., Zhang, M., Feng, D., & Li, M. (2025) · Antioxidants · doi:10.3390/antiox14101230 · Cited by 5
Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives
Li, X., & Qu, S. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-05196-6 · Cited by 5
The Effects of Antioxidant Approved Drugs and Under Investigation Compounds with Potential of Improving Sleep Disorders and their Associated Comorbidities Associated with Oxidative Stress and Inflammation
Theodosis‐Nobelos, P., Varra, F., Varras, M. N., & Rekka, E. A. (2025) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/0113895575360959250117073046 · Cited by 5
Alterations in Skeletal Muscle mRNA Abundance in Response to Ethyl-Cellulose Rumen-Protected Methionine during the Periparturient Period in Dairy Cows
Thanh, L. P., Jiang, Q., Wichasit, N., Batistel, F., Parys, C., Guyader, J., & Loor, J. J. (2022) · Animals · doi:10.3390/ani12131641 · Cited by 5
Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis
Park, J. M., Kim, S., Bae, S. U., Byun, S. J., Seo, I., & Lee, H. W. (2023) · Journal of Korean Medical Science · doi:10.3346/jkms.2023.38.e200 · Cited by 5
Diterpenoid WT-29 isolated from Wedelia exerted anti-inflammatory and anti-allergic activities
Wang, R., Zeng, J., Chen, L., Sun, L., Wang, Y., Xu, J., & He, X. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.117265 · Cited by 5
Microglial Autophagic Dysregulation in Traumatic Brain Injury: Molecular Insights and Therapeutic Avenues
Bano, N., Khan, S., Ahamad, S., Dar, N. J., Alanazi, H. H., Nazir, A., & Bhat, S. A. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00617 · Cited by 6
Nrf2 deficiency causes hepatocyte dedifferentiation and reduced albumin production in an experimental extrahepatic cholestasis model
Wang, G., Garcia, V., Lee, J., Yanum, J. A., Lin, J., Jiang, H., & Dai, G. (2022) · PLoS ONE · doi:10.1371/journal.pone.0269383 · Cited by 5
Expression and localization of NRF2/Keap1 signalling pathway genes in mouse preimplantation embryos exposed to free fatty acids
Dionne, G., Calder, M. D., Betts, D. H., Rafea, B. A., & Watson, A. J. (2022) · Gene Expression Patterns · doi:10.1016/j.gep.2022.119281 · Cited by 5
Artocarmitin B enhances intracellular antioxidant capacity via activation of Nrf2 signaling pathway in human lung epithelial cells
Wu, X., Chen, X.-M., Zhou, M., Hu, H., Zhang, J., Wang, X., Ren, D., Lou, H., & Shen, T. (2019) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2019.108741 · Cited by 5
Cytoprotective Effects of an Aqueous Extracts from Atrina Pectinate Meat in H2O2-Induced Oxidative Stress in a Human Hepatocyte
Shin, E.-J., Han, E. J., Han, H.-J., Jung, K., Heo, S., Kim, E.-A. L., Kim, K., Kim, S.-C., Seo, M.-J., Kwak, I., et al. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-8023-5_58 · Cited by 5
Glutathione Peroxidase 2, a Selenoprotein Exhibiting a Dual Personality in Preventing and Promoting Cancer
Brigelius‐Flohé, R., & Kipp, A. P. (2016) · Springer eBooks · doi:10.1007/978-3-319-41283-2_38 · Cited by 5
Antioxidant Activity In Vitro and Protective Effects Against Lipopolysaccharide-Induced Oxidative Stress and Inflammation in RAW264.7 Cells of Ulva prolifera-Derived Bioactive Peptides Identified by Virtual Screening, Molecular Docking, and Dynamics Simulations
Liu, J., Li, Z., Gu, H., & Shen, S. (2025) · Foods · doi:10.3390/foods14132202 · Cited by 5
The inhibition of TXNRD1 by methylglyoxal impairs the intracellular control of Mycobacterium tuberculosis
Li, H., Liu, R., Kathamuthu, G. R., Gencheva, R., Gong, Z., Scholz, A.-L., Alzrigat, M., Coppo, L., Arnér, E. S. J., & Rottenberg, M. E. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103741 · Cited by 4
Overcoming the Challenge: A Comprehensive Review of Neoadjuvant Treatment Resistance in Rectal Cancer
Micu, A., Diaconescu, A.-S., Minciuna, C.-E., Manuc, T. E., Dima, S., Droc, G., Herlea, V., Becheanu, G., Croitoru, A. E., & Vasilescu, C. (2025) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-025-01324-7 · Cited by 4
The electrophilic metabolite of kynurenine, kynurenine-CKA, requires C151 in Keap1 to derepress Nrf2
Feng, J., Carreño, M., Jung, H., Naidu, S. D., Arroyo-Díaz, N. M., Ang, A. D., Kulkarni, B., Kisielewski, D., Suzuki, T., Yamamoto, M. P., et al. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104009 · Cited by 4
Self-citation
A pharmacological modality to sequester homomeric proteins
Livnah, E., Suss, O., Rogel, A., Gilat, A., Abdan, Y., Villegas, J. A., Gabizon, R., Nadir, A., Shamir, Y., Steinman, N. Y., et al. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02141-0 · Cited by 4
Transcription factor CncC regulates the expression of antennal CYP6MU1 gene responsible for trans-2-hexen-1-al and nonanal recognition in Locusta migratoria
Wu, H., Wang, H., Li, R., Liu, Y., Zhang, Y., Chen, N., Kong, W., Zhao, F., Zhang, X., & Zhang, J. (2023) · Pesticide Biochemistry and Physiology · doi:10.1016/j.pestbp.2023.105620 · Cited by 4
N-acetylcysteine protects against neurodevelopmental injuries induced by methylmercury exposure during pregnancy and lactation
Li, X., Kong, L., Pan, J., Liu, H., Wang, C., Xu, S., Liu, W., & Sun, J. (2024) · Brain Research · doi:10.1016/j.brainres.2024.148761 · Cited by 4
RIN1 regulates ferroptosis and nociceptive perception via the Nrf2/HO-1 pathway in chronic constriction injury
Lin, X., Li, X., Hong, S., Zhou, Q., & You, S. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.111784 · Cited by 4
Tectorigenin alleviates irinotecan-induced intestinal inflammation by activating the Nrf2/Keap1 pathway and synergistically enhances the anti-colon cancer efficacy of irinotecan
Ma, R., Liu, X., Peng, Z. Q., Zou, G., & Zhang, C. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117416 · Cited by 4
Molecular Insights Into Carotenoid‐Based Interventions for Diabetic Retinopathy
Liu, C., Wang, X., Liu, M., & Cao, X. (2025) · Nutrition Bulletin · doi:10.1111/nbu.70015 · Cited by 4
Evaluation of Nrf2/Keap1 Pathway in Patients with Migraine
Koçtürk, F., Emekli, F., Eği, K., & Tayşi, S. (2025) · Medicina · doi:10.3390/medicina61101732 · Cited by 4

Authors: Suzuki, T., & Yamamoto, M.
Affiliations: Tohoku University (JP)
Corresponding author: Yamamoto, Masayuki
ORCID: Suzuki, Takafumi
Yamamoto, Masayuki
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2015-11
Volume: 88
Issue: Pt B
Pages: 93-100
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2015.06.006
OpenAlex: W952491933
Cited by: 995
References: 84
Citations by year: 2026: 62 · 2025: 89 · 2024: 83 · 2023: 102 · 2022: 116 · 2021: 104 · 2020: 118 · 2019: 88 · 2018: 78 · 2017: 82 · 2016: 62 · 2015: 10
FWCI: 7.53
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (am, 360 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Free Radical Biology and Medicine (acceptedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology
Japan Science and Technology Agency
Japan Society for the Promotion of Science (26460354, 2611010, 24249015, 25112502)
Takeda Science Foundation
Naito Foundation
Core Research for Evolutional Science and Technology
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords: Keap1, Nrf2, oxidative stress sensing, electrophilic stress, chemoresistance, carcinogenesis, Nrf2 inhibitors, Nrf2 inducers, therapeutic target
MeSH terms: Animals, Humans, Signal Transduction, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Molecular basis of the Keap1–Nrf2 system

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks