Nrf2 (Nuclear Factor Erythroid 2 Related Factor 2)

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Overview

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 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.

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]), neurodegeneration, and inflammatory bowel disease.

Cross-References

References (9)

  1. Bucciero C, Croce A, Castellano G et al. (2026). The Diet-Multiple Sclerosis Connection: Oxidative Stress and Emerging Mechanisms. Molecular Neurobiology. doi:10.1007/s12035-026-05748-5
  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. doi:10.1038/s41581-020-00345-8
  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. doi:10.1186/s40168-023-01659-y
  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. doi:10.3389/fmicb.2024.1371667
  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. doi:10.1186/s11658-025-00850-3
  6. Natalia Kurhaluk, Piotr Kaminski, Halina Tkaczenko (2025). Kurhaluk 2025 — Oxidative Stress, Antioxidants, Gut Microbiota and Male Fertility. Cellular Physiology and Biochemistry. doi:10.33594/000000802
  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. doi:10.1186/s40168-018-0439-y
  8. Eduardo Duarte-Silva, Sven G. Meuth, Christina Alves Peixoto (2022). Microbial Metabolites in Multiple Sclerosis: Implications for Pathogenesis and Treatment. Frontiers in Neuroscience. doi:10.3389/fnins.2022.885031
  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. doi:10.7759/cureus.47058

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