Nrf2 is a master transcription factor that regulates the expression of antioxidant and cytoprotective genes. It plays a central role in cellular defense against Oxidative Stress, electrophilic stress, and Metal-Driven Inflammation.
Under normal conditions, Nrf2 is sequestered in the cytoplasm by Keap1 and targeted for degradation; under stress, Nrf2 is released and translocates to the nucleus to activate antioxidant response element (ARE)-driven genes.
Evidence map1 cited passagesInspect provenance +
Disease relevance: Nrf2 dysregulation is implicated in multiple sclerosis (), neurodegeneration, and inflammatory bowel disease.
Relevance to WikiBiome#
Metal-Nrf2 interactions: Heavy Metals (cadmium, arsenic, lead) can activate or inhibit Nrf2, depending on dose and chronicity. Acute exposure activates Nrf2 as a defense response; chronic exposure can deplete the Nrf2 pathway.
Microbiome-Nrf2 crosstalk: Gut microbial metabolites (e.g., Butyrate, sulforaphane from dietary sources) can activate Nrf2, while Dysbiosis-associated metabolites may impair it. Disease relevance: Nrf2 dysregulation is implicated in multiple sclerosis ([1]The Diet-Multiple Sclerosis Connection: Oxidative Stress and Emerging MechanismsBucciero C, Croce A, Castellano G et al. · 2026Open reference 1 ↓), neurodegeneration, and inflammatory bowel disease.
Cross-References#
- oxidative stress
- Superoxide Dismutase
- Multiple Sclerosis
- butyrate
References 9
Numbered by first appearance in the article, then reconciled with its declared source list.
- 1
Bucciero C, Croce A, Castellano G et al. (2026). The Diet-Multiple Sclerosis Connection: Oxidative Stress and Emerging Mechanisms. Molecular Neurobiology.
- 2
Denise Mafra, Natalia A. Borges, Bo Lindholm et al. (2021). Food as Medicine: Targeting the Uraemic Phenotype in Chronic Kidney Disease. Nature Reviews Nephrology.
- 3
Zirun Jin, Yuzhuo Yang, Yalei Cao et al. (2023). Jin 2023 — Gut Metabolite 3-HPAA Rejuvenates Spermatogenic Dysfunction in Aged Mice through GPX4-Mediated Ferroptosis. Microbiome.
- 4
Shuya Lv, Jingrong Huang, Yadan Luo et al. (2024). Lv 2024 — Gut Microbiota Is Involved in Male Reproductive Function: A Review. Frontiers in Microbiology.
- 5
Tian M, Zeng X, Zhong Y et al. (2026). Tian et al. 2026 — Tripterygium Glycosides and Lactobacillus paracasei Sensitize EOC to Cisplatin via Keap1-Nrf2-GPX4 Pathway. Cellular and Molecular Biology Letters.
- 6
Natalia Kurhaluk, Piotr Kaminski, Halina Tkaczenko (2025). Kurhaluk 2025 — Oxidative Stress, Antioxidants, Gut Microbiota and Male Fertility. Cellular Physiology and Biochemistry.
- 7
Lesley Hoyles, Tom Snelling, Umm-Kulthum Umlai et al. (2018). Hoyles 2018 — Microbiome-Host Systems Interactions: Protective Effects of Propionate upon the Blood-Brain Barrier. Microbiome.
- 8
Eduardo Duarte-Silva, Sven G. Meuth, Christina Alves Peixoto (2022). Microbial Metabolites in Multiple Sclerosis: Implications for Pathogenesis and Treatment. Frontiers in Neuroscience.
- 9
Mouhammad Sharifa, Tanmay Ghosh, Omar A. Daher et al. (2023). Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights. Cureus.
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