NRF2 / KEAP1

NRF2 is your cells' emergency chief for oxidative stress. It is a transcription factor (a protein that switches genes on) that, once activated, turns on a whole defense program: detox enzymes, glutathione production, proteasome parts, and anti-inflammatory signals. It does this by binding DNA tags called antioxidant response elements (AREs). Most of the time, a partner protein called KEAP1 keeps NRF2 in check by tagging it for destruction (through a CUL3-based disposal system). But when oxidative stress or certain compounds chemically tweak key sulfur sites (cysteines) on KEAP1, KEAP1 loses its grip. NRF2 then piles up and moves into the nucleus to do its job. NRF2 activity drops with age in many tissues, which lets oxidative damage and inflammation build. Compounds like sulforaphane (from broccoli) and other NRF2 activators are being studied to restore that defense. There is a catch, though: a short, hormetic burst of NRF2 seems helpful, while constant activation might feed tumors, so caution is warranted.

Last reviewed: June 22, 2026

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