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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 (bucciero 2026 diet ms oxidative stress nrf2), neurodegeneration, and inflammatory bowel disease.