Nrf2 activation occurs primarily through the disruption of its binding to Keap1. This can be initiated by electrophiles and oxidants that modify critical cysteine residues on Keap1, leading to conformational changes that release Nrf2. Once released, Nrf2 accumulates in the nucleus where it binds to ARE sequences in the promoter regions of target genes, thereby initiating their transcription. These genes encode for enzymes like glutathione S-transferases, NAD(P)H quinone oxidoreductase 1 (NQO1), and others involved in detoxification and antioxidant defense.
