NRF2 restraint
Keap1-Nrf2 clamp
Also searched as Keap1-Nrf2 clamp.
You want this clamp loosened: easing Keap1 frees Nrf2 to raise the body's own antioxidant defenses.
In depth
The molecular clamp that holds the antioxidant master-switch Nrf2 in check until oxidative threat releases it.
What drives it
Oxidative stress reduces it.
Dinkova-Kostova 2002, PNAS 99:11908 — oxidants/electrophiles react with Keap1’s cysteine thiols, disrupting Keap1-Nrf2 and releasing Nrf2. PMID 12193649. ROS is dose-dependent: physiological ROS signals, excess ROS damages. 'Lower ROS' is therefore not universally desirable. Verified, and this is the same event read from the other side: oxidants and electrophiles react with Keap1's reactive cysteines, disabling its ubiquitination activity. Keap1 also acts as a direct H2O2 sensor by forming an intramolecular disulfide bond. PMID 12193649
What it drives
It reduces Antioxidant defense.
Itoh 1999, Genes Dev 13:76 — Keap1 represses Nrf2 via the Neh2 domain; oxidants inactivate Keap1, releasing Nrf2 to the ARE. The limit: the primary (Itoh 1999, Genes Dev 13:76) was not opened; this rests on secondary confirmation only, and remains at ladder T2 rather than T3.
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.