As Nrf2 is phosphorylated through the protein kinase C pathway, it becomes uncoupled from Keap1, leading to enhanced expression of various anti-inflammatory proteins, antioxidant enzymes, and growth factors.111,112 In ischemic stroke, oxidative stress caused by elevated ROS levels induces Nrf2 accumulation in the nucleus, where it binds to antioxidant response elements (ARE) and maintains normal mitochondrial function.113 In contrast, insufficient Nrf2 contributes to neuronal mitochondrial depolarization, ATP depletion, and respiratory function impairment. Here, KEAP1 is linked to ischemic stroke.