Affinage

NFE2L2

Nuclear factor erythroid 2-related factor 2 · UniProt Q16236

Audit flag: ungrounded claim
Length
605 aa
Mass
67.8 kDa
Annotated
2026-06-10
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFE2L2/NRF2 is a stress-responsive transcription factor that binds antioxidant response elements (AREs) in target gene promoters to coordinate antioxidant defense, detoxification, autophagy, and iron/redox metabolism (PMID:27427974). Beyond classical antioxidant enzymes, NFE2L2 directly drives a transcriptional program supporting autophagy: it binds validated AREs in autophagy genes including SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5, and GABARAPL1, with NFE2L2 loss impairing autophagy flux under oxidative stress (PMID:27427974), and it transactivates LAMP2 to control chaperone-mediated autophagy (PMID:29950142). Its activity is governed principally at the protein-stability level through KEAP1: SQSTM1/p62 sequesters KEAP1 into condensates and promotes its autophagic degradation, thereby releasing NFE2L2, a noncanonical activation route that requires SQSTM1 Ser351 phosphorylation by TBK1/ULK1 for the KEAP1-SQSTM1 interaction (PMID:31362587) and that is reinforced by AMPK-coupled feedback driving SQSTM1 expression under metabolic stress (PMID:31913745, PMID:38953910). This SQSTM1-KEAP1 node is further tuned by ubiquitin machinery — SPOP imposes non-degradative ubiquitination on SQSTM1 to restrain NFE2L2 activation (PMID:35438056), while the deubiquitinase USP13 directly stabilizes NFE2L2 to govern an autophagy-to-ferroptosis switch (PMID:39360581). NFE2L2 output also includes a GSH-synthesis program (GCLM/GCLC) feeding mitochondrial glutathione import to suppress cuproptosis (PMID:39609608). Gain-of-function hotspot mutations (E79Q, L30P, R34P) constitutively activate NFE2L2, conferring oncogenicity, radioresistance, immune remodeling, and tumor-type-specific tumorigenesis across hepatoblastoma, HNSCC, and small cell lung cancer (PMID:36652552, PMID:33618031, PMID:35577980). In a separate physiological context, NFE2L2 acts downstream of microglial fractalkine-AKT-GSK3β signaling to induce HMOX1 and limit neuroinflammation (PMID:24277722).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2005 Low

    Established that NRF2 is required for stress-induced antioxidant enzyme induction, framing it as a protective redox effector.

    Evidence nrf-2 gene manipulation and sulforaphane treatment in gastric mucosal cells under H. pylori-associated oxidative injury

    PMID:16259730

    Open questions at the time
    • Abstract-level mechanistic claim lacking experimental detail
    • No direct target genes or binding sites defined
    • Single system, not independently confirmed here
  2. 2011 Medium

    Identified the signaling route to NRF2 activation in a stress context, showing ERK-dependent nuclear translocation drives HO-1.

    Evidence siRNA knockdown, kinase inhibitors, and nuclear translocation assays in cyclosporine-A-treated gingival fibroblasts

    PMID:21622902

    Open questions at the time
    • Does not establish direct ARE binding at HMOX1
    • Mechanism of ERK-NRF2 coupling not defined
    • Single cell type
  3. 2013 High

    Placed NRF2 within an anti-inflammatory neuronal signaling axis, showing it is a required effector downstream of fractalkine in microglia.

    Evidence Nrf2-KO and CX3CR1-KO mice with AAV-TAU(P301L) injection, IHC, Western blot

    PMID:24277722

    Open questions at the time
    • Direct NRF2 targets in microglia beyond HMOX1 not enumerated
    • Does not resolve KEAP1-dependence in this context
  4. 2016 High

    Reframed NRF2 as a direct transcriptional driver of autophagy, not just antioxidant enzymes, by mapping AREs in core autophagy genes.

    Evidence ChIP, qRT-PCR, NFE2L2 KO MEFs with lentiviral rescue, autophagy flux assays in human and mouse cells

    PMID:27427974

    Open questions at the time
    • Does not address feedback via SQSTM1 it transcribes
    • Quantitative contribution of each ARE not dissected
  5. 2018 High

    Extended NRF2 transcriptional control to chaperone-mediated autophagy by identifying LAMP2 as a direct target.

    Evidence ChIP, qRT-PCR, NFE2L2 KO hepatocytes, gain-of-function and pharmacological activation, CMA activity assays

    PMID:29950142

    Open questions at the time
    • LAMP2A-specific isoform regulation mechanism not fully resolved
    • Single tissue context
  6. 2019 High

    Defined the molecular requirement for noncanonical NRF2 activation, showing SQSTM1 Ser351 phosphorylation gates the KEAP1-SQSTM1 interaction.

    Evidence Co-IP, site-specific phospho-mutant constructs, ALS-FTLD SQSTM1 mutant, gene expression assays in neuronal cells

    PMID:31362587

    Open questions at the time
    • Relative contributions of TBK1 vs ULK1 not quantified
    • Structural basis of phospho-dependent binding not solved
  7. 2020 High

    Established the epistatic logic of noncanonical activation: SQSTM1 drives AMPK-ULK1-dependent autophagic KEAP1 degradation to release NRF2.

    Evidence Co-IP, phosphorylation assays, sqstm1 conventional and liver-specific KO mice under lipotoxic conditions

    PMID:31913745

    Open questions at the time
    • Does not quantify KEAP1 turnover kinetics
    • Generality beyond hepatic lipotoxicity
  8. 2021 Medium

    Demonstrated that NRF2 hotspot mutations are intrinsically oncogenic and remodel the tumor immune microenvironment.

    Evidence Nrf2E79Q HNSCC lines and syngeneic vs immunocompromised mice with flow cytometry; hydrodynamic transfection of L30P/R34P mutants in murine liver

    PMID:33618031 PMID:36652552

    Open questions at the time
    • Direct transcriptional targets mediating immune remodeling only partly defined
    • Single-lab in vivo models
  9. 2022 High

    Identified post-transcriptional control of NRF2 via m6A, showing ALKBH5 demethylation destabilizes NFE2L2 mRNA in an IGF2BP2-dependent manner.

    Evidence MeRIP-seq, RIP-seq, dual-luciferase reporter, ALKBH5 knockdown in hypopharyngeal carcinoma cells

    PMID:35689537

    Open questions at the time
    • In vivo relevance not tested
    • Stoichiometry of the two 3'-UTR m6A sites unresolved
  10. 2022 Medium

    Showed in Drosophila that loss of selective autophagy activates the NRF2 ortholog via Keap1 co-sequestration, providing cross-species support for the SQSTM1-KEAP1 axis.

    Evidence ref(2)P LIR-motif point mutant, Keap1 co-sequestration assay, oxidative stress and mitochondrial superoxide measurements

    PMID:35184662

    Open questions at the time
    • Ortholog system; human equivalence not directly shown
    • Single lab
  11. 2024 Medium

    Resolved ubiquitin-machinery control of the SQSTM1-KEAP1-NRF2 node from both directions: SPOP restrains it via non-degradative SQSTM1 ubiquitination, while USP13 directly deubiquitinates and stabilizes NRF2.

    Evidence SPOP binding/ubiquitination assays with SQSTM1 K420 mutants and condensation assays; DUB screen, Co-IP, ubiquitination assays, USP13 KD in vitro and xenografts

    PMID:35438056 PMID:39360581

    Open questions at the time
    • USP13 deubiquitination established High; SPOP node Medium/single lab
    • Crosstalk between SPOP and USP13 on NRF2 not tested together
  12. 2024 Medium

    Connected NRF2 output to metabolic cell-death control via a GSH-synthesis program and integrated it into an AMPK feedback loop.

    Evidence NFE2L2 stability assays with GCLM/GCLC and SLC25A39 in PDAC cuproptosis models; SQSTM1 phospho-mapping (S24/S226 by TAK1) with AMPK and TFEB/TFE3 readouts in NSCLC

    PMID:38953910 PMID:39609608

    Open questions at the time
    • NFE2L2 stabilization mechanism by ES-Cu not biochemically dissected
    • Generality of the double-positive feedback loop beyond NSCLC
  13. 2024 Medium

    Refined oncogenic context-dependence, showing NRF2 hotspot activation promotes specific tumor subtypes.

    Evidence Trp53/p16-deficient GEMM with conditional LSL-Nrf2E79Q activation, histopathology and pathway signature analysis

    PMID:35577980

    Open questions at the time
    • Mechanism of subtype selectivity (P-SCLC vs C-SCLC) unexplained
    • Single GEMM

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple layers of NRF2 control — KEAP1 sequestration, m6A mRNA stabilization, USP13/SPOP ubiquitin editing, and AMPK feedback — are integrated and prioritized within a single cell under graded stress remains unresolved.
  • No unified quantitative model of relative flux through each regulatory layer
  • Structural basis of NRF2-ARE selectivity across antioxidant vs autophagy targets not defined
  • Therapeutic exploitation of activating mutations beyond glutaminase inhibition untested broadly

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-9612973 Autophagy 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
KEAP1SQSTM1USP13

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 NFE2L2/NRF2 directly regulates transcription of autophagy-related genes by binding antioxidant response elements (AREs) in their promoters. ChIP assays and qRT-PCR on human and mouse cells validated 12 AREs in 9 autophagy genes (including SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5, GABARAPL1). Loss of NFE2L2 in knockout MEFs reduced autophagy gene expression and impaired autophagy flux under oxidative stress, rescued by NFE2L2-expressing lentivirus. ChIP (ENCODE database + experimental), qRT-PCR, NFE2L2 knockout MEFs, lentiviral rescue, autophagy flux assays Autophagy High 27427974
2018 NFE2L2/NRF2 transcriptionally regulates LAMP2A by binding two validated ARE sequences in the LAMP2 gene, thereby controlling chaperone-mediated autophagy (CMA) activity. NFE2L2 deficiency reduced lysosomal LAMP2A levels and CMA activity in hepatocytes; overexpression or pharmacological activation (sulforaphane, dimethyl fumarate) increased both LAMP2A and CMA activity. ChIP, qRT-PCR, NFE2L2 KO hepatocytes, NFE2L2 overexpression, pharmacological activation, CMA activity assays Autophagy High 29950142
2020 SQSTM1/p62 activates NFE2L2 through a noncanonical pathway: SQSTM1 facilitates AMPK-ULK1 interaction, leading to ULK1 phosphorylation, macroautophagy induction, and autophagic KEAP1 degradation, thereby releasing NFE2L2. Demonstrated in hepatocytes under lipotoxic conditions and confirmed in sqstm1-knockout mice. Co-immunoprecipitation, phosphorylation assays, sqstm1 conventional and liver-specific KO mice, autophagic flux assays, Western blot Autophagy High 31913745
2019 SQSTM1 Ser351 phosphorylation is required for KEAP1-SQSTM1 interaction and NFE2L2 activation. ALS-FTLD-linked mutation SQSTM1G427R abolishes Ser351 phosphorylation, disrupts the KEAP1-SQSTM1 interaction, and diminishes NFE2L2-targeted gene expression under oxidative stress. TBK1 and ULK1 coordinately phosphorylate SQSTM1 to promote selective autophagy and NFE2L2 signaling. Immunoprecipitation, phosphorylation assays with mutant constructs, gene expression analysis, neuronal overexpression experiments Autophagy High 31362587
2013 In microglia, fractalkine signaling activates AKT, inhibits GSK-3β, and upregulates NFE2L2/NRF2 and its target gene heme oxygenase 1 (HMOX1). NRF2-knockout and fractalkine receptor-knockout mice failed to express HMOX1 in microglia and showed increased microgliosis/astrogliosis in response to neuronal TAU(P301L), establishing NRF2 as a required component of the fractalkine anti-inflammatory pathway. Genetic KO mouse models (Nrf2-KO, CX3CR1-KO), AAV-TAU(P301L) hippocampal injection, immunohistochemistry, Western blot Brain High 24277722
2022 ALKBH5-mediated m6A demethylation at two m6A residues in the 3'-UTR of NFE2L2 mRNA leads to post-transcriptional inhibition of NFE2L2/NRF2. m6A-dependent stabilization of NFE2L2 mRNA requires the reader protein IGF2BP2. Knockdown of ALKBH5 increases NFE2L2 expression and ferroptosis resistance in hypopharyngeal squamous cell carcinoma cells. m6A-seq (MeRIP-seq), RNA-seq, RIP-seq, MeRIP-qPCR, RIP-qPCR, dual-luciferase reporter assay, ALKBH5 knockdown Journal of clinical laboratory analysis High 35689537
2024 USP13 deubiquitinase interacts with and catalyzes deubiquitination of NFE2L2, stabilizing its protein levels. USP13 depletion promotes an autophagy-to-ferroptosis switch through the NFE2L2-SQSTM1/p62-KEAP1 axis in KRAS-mutant lung adenocarcinoma cells and xenograft models. DUB screen (85 enzymes), Co-IP, ubiquitination assays, USP13 KD in vitro and xenograft mouse models, NFE2L2 protein stability assays Autophagy High 39360581
2024 ES-Cu (elesclomol plus copper) increases NFE2L2 protein stability, leading to upregulation of GCLM and GCLC (rate-limiting enzymes in GSH synthesis). Elevated GSH is then transported into mitochondria via SLC25A39 to inhibit cuproptosis. Genetic inhibition of the NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis in PDAC cells and mouse tumor models. NFE2L2 protein stability assays, gene expression analysis, genetic inhibition (KO/KD), cell culture cuproptosis assays, mouse tumor models Scientific reports Medium 39609608
2024 SPOP E3 ubiquitin ligase adaptor binds SQSTM1 and induces non-degradative ubiquitination at Lys420, which suppresses SQSTM1 body formation and KEAP1 sequestration, thereby inhibiting NFE2L2 activation. Cancer-associated SPOP mutants lose the capacity to ubiquitinate SQSTM1 and instead enhance NFE2L2 activation in a dominant-negative manner. Binding assays, ubiquitination assays, SQSTM1 Lys420 mutant constructs, liquid phase condensation assays, SQSTM1 dimerization assays Autophagy Medium 35438056
2024 Metabolic stress induces a double-positive feedback loop: SQSTM1 phosphorylation (at S24 and S226 by MAP3K7/TAK1) activates both AMPK (by facilitating AXIN-STK11-AMPK complex on lysosomal membrane) and NFE2L2 (via autophagic KEAP1 degradation). AMPK activity in turn drives SQSTM1 expression through TFEB/TFE3 dephosphorylation. This synergizes antioxidant defense in NSCLC. Co-IP, phosphorylation mapping with phospho-specific antibodies, SQSTM1 phospho-mutant constructs, autophagy flux assays, MEF experiments, lysosomal fractionation Autophagy High 38953910
2022 In Drosophila, disruption of ubiquitinated protein autophagy (ref(2)P/SQSTM1 mutation that prevents Atg8a binding) causes polyubiquitinated aggregate accumulation that co-sequesters Keap1, thereby activating the cnc/NFE2L2/Nrf2 antioxidant pathway. This activation increases oxidative stress tolerance and reduces mitochondrial superoxide, compensating for lost autophagy. Drosophila genetic model, ref(2)P point mutant (disrupted LIR motif), Keap1 co-sequestration assay, oxidative stress tolerance assay, mitochondrial superoxide measurement Autophagy Medium 35184662
2021 NFE2L2 mutation (Nrf2E79Q) activates Nrf2, confers radioresistance in HNSCC cells, and promotes recruitment of PMN-MDSCs while reducing M1-polarized macrophages in immunocompetent but not immunocompromised mice. Glutaminase inhibition (CB-839) overcomes this radioresistance by reversing CXCL1/CXCL3/CSF3 upregulation via TLR4. HNSCC cell lines with Nrf2E79Q/E79K mutants, syngeneic immunocompetent vs. immunocompromised mouse tumors, flow cytometry, CB-839 pharmacological treatment, cytokine expression analysis Cancer research Medium 36652552
2021 Patient-derived NFE2L2 mutants (L30P and R34P) are directly oncogenic in mouse liver: co-expression of any two members of the mutant β-catenin–YAPS127A–NFE2L2-mutant triad is sufficient to drive hepatoblastoma growth, establishing NFE2L2 oncogenicity independent of its co-drivers. Hydrodynamic transfection into murine liver, tumor growth measurement, transcriptomic analysis, survival correlation in human HB datasets Cellular and molecular gastroenterology and hepatology Medium 33618031
2022 In Trp53/p16-deficient mice, activation of the NRF2E79Q mutation is associated with increased incidence of pure-SCLC (P-SCLC) but not combined-SCLC (C-SCLC), suggesting a tumor-type-specific oncogenic role for NRF2 activation in small cell lung cancer development. Genetically engineered mouse model (GEMM), Cre-induced LSL-Nrf2E79Q recombination, histopathology, IHC, NRF2 pathway signature analysis Oncogene Medium 35577980
2011 Cyclosporine-A (CsA)-stimulated HO-1 expression in human gingival fibroblasts is mediated through ERK-dependent nuclear translocation of NFE2L2/NRF2. siRNA knockdown of Nrf-2 (but not NF-κB inhibition) reduced CsA-stimulated HO-1 mRNA expression; ERK inhibition decreased NRF2 nuclear translocation and HO-1 expression. siRNA knockdown, kinase inhibitors, nuclear translocation assay, qRT-PCR, sulforaphane pretreatment Journal of dental research Medium 21622902
2005 The nrf-2 gene is required for induction of antioxidant enzymes in gastric mucosal cells exposed to oxidative stress. Sulforaphane stimulates nrf-2-gene-dependent antioxidant enzyme activities, protecting gastric cells from oxidative injury during H. pylori infection. Cell-based antioxidant enzyme activity assays, nrf-2 gene manipulation, sulforaphane treatment, mucosal cell protection assays Inflammopharmacology Low 16259730

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes. Autophagy 331 27427974
2020 SQSTM1/p62 activates NFE2L2/NRF2 via ULK1-mediated autophagic KEAP1 degradation and protects mouse liver from lipotoxicity. Autophagy 191 31913745
2018 Regulatory crosstalk between the oxidative stress-related transcription factor Nfe2l2/Nrf2 and mitochondria. Toxicology and applied pharmacology 190 30236989
2018 Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through the regulation of LAMP2A. Autophagy 183 29950142
2019 ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway. Autophagy 182 31362587
2020 The Nrf-2/HO-1 Signaling Axis: A Ray of Hope in Cardiovascular Diseases. Cardiology research and practice 148 32411446
2013 Fractalkine activates NRF2/NFE2L2 and heme oxygenase 1 to restrain tauopathy-induced microgliosis. Brain : a journal of neurology 141 24277722
2018 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC). Clinical cancer research : an official journal of the American Association for Cancer Research 129 29615460
2012 Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity. Cell stress & chaperones 127 22362068
2021 Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain. Autophagy 107 33834930
2017 Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy. Toxicology reports 105 28959654
2022 Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation. International journal of molecular sciences 95 35409364
2019 Mutations in the KEAP1-NFE2L2 Pathway Define a Molecular Subset of Rapidly Progressing Lung Adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 75 31323387
2018 Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer. Cancers 75 30257470
2022 Fetuin-A alleviates neuroinflammation against traumatic brain injury-induced microglial necroptosis by regulating Nrf-2/HO-1 pathway. Journal of neuroinflammation 69 36333786
2020 Clinical Implications of KEAP1-NFE2L2 Mutations in NSCLC. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 69 33307193
2018 Targeting Nrf-2 is a promising intervention approach for the prevention of ethanol-induced liver disease. Cellular and molecular life sciences : CMLS 66 29947925
2014 Genetic associations of Nrf2-encoding NFE2L2 variants with Parkinson's disease - a multicenter study. BMC medical genetics 65 25496089
2023 NFE2L2 Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells. Cancer research 57 36652552
2023 Cigarette smoke induces the ROS accumulation and iNOS activation through deactivation of Nrf-2/SIRT3 axis to mediate the human bronchial epithelium ferroptosis. Free radical biology & medicine 55 36871899
2019 The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology. International journal of molecular sciences 53 31752195
2022 RNA demethylase ALKBH5 regulates hypopharyngeal squamous cell carcinoma ferroptosis by posttranscriptionally activating NFE2L2/NRF2 in an m6 A-IGF2BP2-dependent manner. Journal of clinical laboratory analysis 50 35689537
2022 Icariin protects vertebral endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 pathway. Frontiers in pharmacology 50 36176424
2024 NFE2L2 and ferroptosis resistance in cancer therapy. Cancer drug resistance (Alhambra, Calif.) 49 39534872
2017 Effects of Estradiol on Autophagy and Nrf-2/ARE Signals after Cerebral Ischemia. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 49 28419990
2018 Dimethyl fumarate ameliorates acetaminophen-induced hepatic injury in mice dependent of Nrf-2/HO-1 pathway. Life sciences 41 30550888
2024 NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism. Scientific reports 38 39609608
2021 Probucol attenuates NF-κB/NLRP3 signalling and augments Nrf-2 mediated antioxidant defence in nerve injury induced neuropathic pain. International immunopharmacology 38 34891000
2023 Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway. International immunopharmacology 37 37054647
2020 NRF-2 and nonalcoholic fatty liver disease. Annals of hepatology 37 31959521
2020 RETRACTED: Piperine Regulates Nrf-2/Keap-1 Signalling and Exhibits Anticancer Effect in Experimental Colon Carcinogenesis in Wistar Rats. Biology 37 32967203
2021 KEAP1/NRF2 (NFE2L2) mutations in NSCLC - Fuel for a superresistant phenotype? Lung cancer (Amsterdam, Netherlands) 36 34303275
2020 Nrf-2 as a therapeutic target in acute kidney injury. Life sciences 35 33065149
2017 Nrf-2-driven long noncoding RNA ODRUL contributes to modulating silver nanoparticle-induced effects on erythroid cells. Biomaterials 35 28351005
2022 Targeting NFE2L2/KEAP1 Mutations in Advanced NSCLC With the TORC1/2 Inhibitor TAK-228. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 33 36240971
2024 Quercetin Modulates Ferroptosis via the SIRT1/Nrf-2/HO-1 Pathway and Attenuates Cartilage Destruction in an Osteoarthritis Rat Model. International journal of molecular sciences 32 39000568
2021 Therapeutic potential of Nrf-2 pathway in the treatment of diabetic neuropathy and nephropathy. Molecular biology reports 31 33754251
2014 NFE2L2 polymorphisms, mortality, and metabolism in the general population. Physiological genomics 31 24790085
2016 Daphnetin ameliorates 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis through Nrf-2-Keap1 and NF-κB pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 27470383
2021 Oleoylethanolamide Protects Against Acute Liver Injury by Regulating Nrf-2/HO-1 and NLRP3 Pathways in Mice. Frontiers in pharmacology 29 33536915
2021 Oridonin prevents oxidative stress-induced endothelial injury via promoting Nrf-2 pathway in ischaemic stroke. Journal of cellular and molecular medicine 29 34514714
2020 MicroRNAs as regulators of VEGFA and NFE2L2 in cancer. Gene 29 32721475
2020 MicroRNA-153-3p regulates cell proliferation and cisplatin resistance via Nrf-2 in esophageal squamous cell carcinoma. Thoracic cancer 28 32012470
2024 Baicalin inhibits IL-1β-induced ferroptosis in human osteoarthritis chondrocytes by activating Nrf-2 signaling pathway. Journal of orthopaedic surgery and research 27 38166985
2022 Molecular mechanisms regulating the pharmacological actions of icariin with special focus on PI3K-AKT and Nrf-2 signaling pathways. Molecular biology reports 27 35941411
2020 Esculetin protects human corneal epithelial cells from oxidative stress through Nrf-2 signaling pathway. Experimental eye research 27 33220236
2024 USP13 facilitates a ferroptosis-to-autophagy switch by activation of the NFE2L2/NRF2-SQSTM1/p62-KEAP1 axis dependent on the KRAS signaling pathway. Autophagy 26 39360581
2023 Activation of the Nrf-2 pathway by pinocembrin safeguards vertebral endplate chondrocytes against apoptosis and degeneration caused by oxidative stress. Life sciences 26 37820754
2023 β-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury. Molecular medicine (Cambridge, Mass.) 26 38049750
2017 Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA. Current cardiology reviews 26 28215178
2005 Role of the nrf-2 gene in protection and repair of gastric mucosa against oxidative stress. Inflammopharmacology 26 16259730
2024 Metabolic stress induces a double-positive feedback loop between AMPK and SQSTM1/p62 conferring dual activation of AMPK and NFE2L2/NRF2 to synergize antioxidant defense. Autophagy 25 38953310
2015 NT-020 treatment reduces inflammation and augments Nrf-2 and Wnt signaling in aged rats. Journal of neuroinflammation 25 26376629
2022 Enhanced autophagy and NFE2L2/NRF2 pathway activation in SPOP mutation-driven prostate cancer. Autophagy 24 35438056
2020 La2O3 Nanoparticles Induce Reproductive Toxicity Mediated by the Nrf-2/ARE Signaling Pathway in Kunming Mice. International journal of nanomedicine 24 32523341
2024 Clobetasol propionate, a Nrf-2 inhibitor, sensitizes human lung cancer cells to radiation-induced killing via mitochondrial ROS-dependent ferroptosis. Acta pharmacologica Sinica 23 38480835
2023 Bdnf-Nrf-2 crosstalk and emotional behavior are disrupted in a sex-dependent fashion in adolescent mice exposed to maternal stress or maternal obesity. Translational psychiatry 23 38105264
2020 Mesenchymal stem cell exosomes reverse acute lung injury through Nrf-2/ARE and NF-κB signaling pathways. PeerJ 23 32999767
2015 What is Known Regarding the Participation of Factor Nrf-2 in Liver Regeneration? Cells 23 26010752
2010 NFE2L2 gene mutation in male Japanese squamous cell carcinoma of the lung. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 23 20421815
2014 Elevated Expression of Nrf-2 and ABCG2 Involved in Multi-drug Resistance of Lung Cancer SP Cells. Drug research 22 25368906
2021 Patient-Derived Mutant Forms of NFE2L2/NRF2 Drive Aggressive Murine Hepatoblastomas. Cellular and molecular gastroenterology and hepatology 21 33618031
2021 Wogonin Inhibits Cardiac Hypertrophy by Activating Nrf-2-Mediated Antioxidant Responses. Cardiovascular therapeutics 21 34290825
2020 Imperatorin Relieved Ulcerative Colitis by Regulating the Nrf-2/ARE/HO-1 Pathway in Rats. Inflammation 21 33098052
2019 Gastrodin alleviates Tourette syndrome via Nrf-2/HO-1/HMGB1/NF-кB pathway. Journal of biochemical and molecular toxicology 21 31468582
2016 Plumbagin protects against hydrogen peroxide-induced neurotoxicity by modulating NF-κB and Nrf-2. Archives of medical science : AMS 21 30154895
2015 Plumbagin protects against glucocorticoid-induced osteoporosis through Nrf-2 pathway. Cell stress & chaperones 21 25939783
2023 KEAP1/NFE2L2 Pathway Signature Outperforms KEAP1/NFE2L2 Mutation Status and Reveals Alternative Pathway-Activating Mutations in NSCLC. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20 37473958
2022 TP53, CDKN2A/P16, and NFE2L2/NRF2 regulate the incidence of pure- and combined-small cell lung cancer in mice. Oncogene 20 35577980
2022 Pharmacological mechanism of xanthoangelol underlying Nrf-2/TRPV1 and anti-apoptotic pathway against scopolamine-induced amnesia in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 35658216
2023 Mitigative potential of kaempferide against polyethylene microplastics induced testicular damage by activating Nrf-2/Keap-1 pathway. Ecotoxicology and environmental safety 19 38035520
2021 Astaxanthin attenuates acute cerebral infarction via Nrf-2/HO-1 pathway in rats. Current research in translational medicine 19 33476935
2021 Activated Nrf-2 Pathway by Vitamin E to Attenuate Testicular Injuries of Rats with Sub-chronic Cadmium Exposure. Biological trace element research 19 34173155
2015 Esculentoside A Attenuates Allergic Airway Inflammation via Activation of the Nrf-2 Pathway. International archives of allergy and immunology 19 26496193
2023 Combination of metformin and hesperidin mitigates cyclophosphamide-induced hepatotoxicity. Emerging role of PPAR-γ/Nrf-2/NF-κB signaling pathway. International immunopharmacology 17 36812672
2022 Nicotinic Acid Riboside Regulates Nrf-2/P62-Related Oxidative Stress and Autophagy to Attenuate Doxorubicin-Induced Cardiomyocyte Injury. BioMed research international 17 35242876
2018 δ-Opioid Receptor-Nrf-2-Mediated Inhibition of Inflammatory Cytokines in Neonatal Hypoxic-Ischemic Encephalopathy. Molecular neurobiology 17 30560518
2011 Nrf-2 regulates cyclosporine-stimulated HO-1 expression in gingiva. Journal of dental research 17 21622902
2021 Upregulation of NOX-2 and Nrf-2 Promotes 5-Fluorouracil Resistance of Human Colon Carcinoma (HCT-116) Cells. Biochemistry. Biokhimiia 16 33838628
2018 Exenatide Increases IL-1RA Concentration and Induces Nrf-2‒Keap-1‒Regulated Antioxidant Enzymes: Relevance to β-Cell Function. The Journal of clinical endocrinology and metabolism 16 29346597
2024 Mechanistic insights on the role of Nrf-2 signalling in Huntington's disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 15 39392523
2022 Loss of ubiquitinated protein autophagy is compensated by persistent cnc/NFE2L2/Nrf2 antioxidant responses. Autophagy 15 35184662
2022 Protection Against Drug-Induced Liver Injuries Through Nutraceuticals via Amelioration of Nrf-2 Signaling. Journal of the American Nutrition Association 15 35771985
2021 Second-hand smoke and NFE2L2 genotype interaction increases paediatric asthma risk and severity. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 15 33382170
2024 Palladium nanocrystals regulates scleral extracellular matrix remodeling in myopic progression by modulating the hypoxia signaling pathway Nrf-2/Ho-1. Journal of controlled release : official journal of the Controlled Release Society 14 39019088
2022 Regulation of VEGFA, KRAS, and NFE2L2 Oncogenes by MicroRNAs in Head and Neck Cancer. International journal of molecular sciences 14 35806488
2021 Astaxanthin Relieves Busulfan-Induced Oxidative Apoptosis in Cultured Human Spermatogonial Stem Cells by Activating the Nrf-2/HO-1 pathway. Reproductive sciences (Thousand Oaks, Calif.) 14 34129218
2021 Small-molecule Akt-activation in airway cells induces NO production and reduces IL-8 transcription through Nrf-2. Respiratory research 14 34666758
2012 NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease. Physiological genomics 14 22693272
2023 β-Endorphin (an endogenous opioid) inhibits inflammation, oxidative stress and apoptosis via Nrf-2 in asthmatic murine model. Scientific reports 13 37524754
2023 Chitosan-insulin nano-formulations as critical modulators of inflammatory cytokines and Nrf-2 pathway to accelerate burn wound healing. Discover nano 13 38087141
2022 Nfe2l2 Regulates Metabolic Rewiring and Epigenetic Reprogramming in Mediating Cancer Protective Effect by Fucoxanthin. The AAPS journal 13 35043283
2022 A Nrf-2 Stimulatory Hydroxylated Cannabidiol Derivative from Hemp (Cannabis sativa). Journal of natural products 13 35316044
2022 Coagulansin-A improves spatial memory in 5xFAD Tg mice by targeting Nrf-2/NF-κB and Bcl-2 pathway. International immunopharmacology 13 35598479
2021 AOPPs induce HTR-8/SVneo cell apoptosis by downregulating the Nrf-2/ARE/HO-1 anti-oxidative pathway: Potential implications for preeclampsia. Placenta 13 34237527
2024 Capsaicin ameliorate pulmonary fibrosis via antioxidant Nrf-2/ PPAR- γ pathway activation and inflammatory TGF-β1/ NF-κB/COX II pathway inhibition. Frontiers in pharmacology 12 38449809
2024 Nrf-2 as a novel target in radiation induced lung injury. Heliyon 12 38665580
2021 Integrated analysis of patients with KEAP1/NFE2L2/CUL3 mutations in lung adenocarcinomas. Cancer medicine 12 34617407
2018 NFE2L2, PPARGC1α, and pesticides and Parkinson's disease risk and progression. Mechanisms of ageing and development 12 29630901
2018 Elevated Nrf-2 responses are insufficient to mitigate protein carbonylation in hepatospecific PTEN deletion mice. PloS one 12 29799837

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