nuclear factor erythroid 2-related factor 2

Overview

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in cellular defense against oxidative stress and inflammation. It regulates the expression of various antioxidant genes and enzymes, including heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), through its interaction with the antioxidant response element (ARE) in the promoter regions of target genes. Nrf2 is essential for maintaining cellular homeostasis and protecting against damage caused by reactive oxygen species (ROS). Dysregulation of Nrf2 signaling has been implicated in various diseases, including cancer, neurodegenerative disorders, and metabolic dysfunctions, making it a significant target for therapeutic interventions.

Focus of Latest Publications

Recent studies have highlighted the multifaceted role of Nrf2 in various pathological contexts. For instance, a study published in Redox Report (PMID: 42046449) elucidated the protective role of quercetin against lipopolysaccharide-induced necroptosis in broiler thymus, demonstrating that Nrf2 can initiate the protein kinase RNA-like ER kinase (PERK) pathway, which is linked to immune dysfunction. Another study in Renal Failure (PMID: 41912450) reported that recombinant human ADAMTS13 ameliorated diabetic nephropathy by activating the Nrf2/GPX4 signaling pathway, thereby inhibiting ROS generation and mitigating renal injury in diabetic mice.

In the context of neurodegenerative diseases, research published in Bioorganic Chemistry (PMID: 41797134) showed that Nrf2 was downregulated alongside apoptotic proteins in models of septic acute kidney injury, indicating its potential role in mitochondrial restoration and oxidative stress reduction. Furthermore, a study in The Journal of Pathology (PMID: 41944556) emphasized the importance of the Nrf2-KEAP1 axis in understanding the biological heterogeneity of Nrf2 pathway dysregulation in clinical settings.

Nrf2's involvement in ferroptosis, a form of regulated cell death, was also explored in several studies. For example, research in European Journal of Pharmacology (PMID: 42044765) demonstrated that inhibiting ferroptosis via the Nrf2/HO-1 pathway exerted renal protective effects in membranous nephropathy rats. Similarly, a study in Food & Function (PMID: 42132559) indicated that Noni fruit juice induced ferroptosis in gastric cancer cells through the Nrf2/HO-1-GPX4 axis, highlighting Nrf2's critical role in cancer biology.

Additionally, various natural compounds, such as avenanthramide C from oat sprout extract (PMID: 42102478) and yellow tea extract (PMID: 42207030), were shown to activate Nrf2, promoting antioxidant responses and improving cellular resilience against oxidative stress. These findings collectively underscore the significance of Nrf2 in mediating protective responses across different biological systems and its potential as a therapeutic target in various diseases.

Key Publications

• Jun Poliumoside alleviates oxidative stress and improves mitochondrial function to alleviate ischemic stroke injury. (European journal of pharmacology, 2026, PMID 42134761): "Mechanistically, POL activated the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway antioxidant pathway, promoting Nrf2 nuclear translocation and upregulating downstream proteins Heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1)."
• Jun Protection of skin from UVB-induced photoaging: Antioxidant and anti-inflammatory effects of avenanthramide C from oat sprout extract via suppression of MAPK pathways. (Journal of photochemistry and photobiology. B, Biology, 2026, PMID 42102478): "AVN C reduced oxidative stress by promoting the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and upregulating antioxidant enzyme expression."
• May Yellow tea extract ameliorates dexamethasone-induced hepatic steatosis by modulating the gut-liver axis and reshaping microbial metabolites: a multi-omics insight. (Food & function, 2026, PMID 42207030): "Hepatic transcriptomics and subsequent reverse transcription quantitative PCR (RT-qPCR) validation revealed that YT upregulated the antioxidant genes nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) while downregulating the lipogenic gene sterol regulatory element-binding protein 1c (SREBP-1c) and upregulating the fatty acid oxidation gene peroxisome proliferator-activated receptor alpha (PPAR-α)."
• May Inhibition of ferroptosis exerts renal protective effects in membranous nephropathy rats via the Nrf2/HO-1 pathway. (European journal of pharmacology, 2026, PMID 42044765): "This study investigated whether the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway mediates MN progression via ferroptosis."
• May Noni (Morinda citrifolia L.) fruit juice induces ferroptosis in gastric cancer cells via the Nrf2/HO-1-GPX4 axis. (Food & function, 2026, PMID 42132559): "Pharmacological activation leads to the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus."
• Apr Hepatoprotective potential of anthocyanins from purple highland barley bran against non-alcoholic fatty liver disease through gut-liver axis. (Food research international (Ottawa, Ont.), 2026, PMID 41794448): "the underlying mechanism was partially involved in the activation of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway and inhibition of p38 mitogen-activated protein kinase (MAPK) pathway."
• Apr Elucidating the protective role of quercetin against lipopolysaccharide-induced necroptosis in broiler thymus: insights from Nrf2/PERK signaling based on network pharmacology and experimental validation. (Redox report : communications in free radical research, 2026, PMID 42046449): "Nuclear factor erythroid 2-related factor 2 (Nrf2) can initiate protein kinase RNA-like ER kinase (PERK), leading to immune dysfunction and necroptosis."
• Apr Inhibiting NAT10 suppresses hepatocellular carcinoma progression by reducing Nrf2 mRNA stability and increasing oxidative stress. (Chemico-biological interactions, 2026, PMID 41692399): "We show that NAT10 stabilizes Nrf2 mRNA, a master regulator of antioxidant responses, thereby maintaining Nrf2 protein abundance and reducing intracellular reactive oxygen species (ROS) levels in HCC cells."
• Apr The NRF2 readout beyond genotyping†. (The Journal of pathology, 2026, PMID 41944556): "Until now, clinical and translational efforts have largely focused on recurrent genomic alterations in the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (NRF2) axis, yet mutation status alone often fails to capture the biological heterogeneity and context dependence of NRF2 pathway dysregulation."
• Apr Curcumin-Loaded Liposomes (hPLipo/Cur) with Liver-Targeting Properties for Efficient NAFLD Treatment by Alleviating Mitochondrial ROS-Mediated Ferroptosis via NRF2 Pathway. (Molecular pharmaceutics, 2026, PMID 41725216): "Mechanistically, hPLipo/Cur reduces NRF2 degradation and promotes the nuclear translocation of NRF2, as well as the expression of downstream antioxidant genes."