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Normally, the transcription factor Nrf2 and its inhibitory protein KEAP1 are tightly bound to inhibit activity, but in the presence of ROS, a conformational change in KEAP1 results in the release of NRF2, which binds to the antioxidant response element (ARE) and activates the downstream genes heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), quinone oxidoreductase1(NQO1), thioredoxin reductase 1 (SRXN1), and transcription of solute carrier family 7 member 11 (SLC7A11), which enhance cellular antioxidant defenses and inhibit ferroptosis (Wang et al., 2022
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