Potential Effects of Nrf2 in Exercise Intervention of Neurotoxicity Caused by Methamphetamine Oxidative Stress

Figure 2

Keap1-Nrf2 pathway during constitutive and activative status. Nrf2 is adhered in the cytoplasm by Keap1 under normal physiological conditions. Keap1, as a substrate of the Cullin 3- (Cul3-) dependent E3 ubiquitin ligase complex, promotes Nrf2 ubiquitination and is rapidly hydrolyzed by the proteasome. While cells are attacked by ROS, Nrf2 dissociates from Keap1 and migrates rapidly to the nucleus. It first forms heterodimers with Maf proteins, then binds to antioxidant response elements (AREs), and regulates transcriptional activation of antioxidant oxidase gene expression. In addition, Nrf2 also has alternative activation pathways, which are regulated by phosphorylation, PKC, PI3K/Akt, and JNK to further alter the transcriptional activation of antioxidant genes. miRNA was also found to enhance Nrf2 activity by inhibiting Keap1 expression. Adapted from “Keap1-Nrf2 pathway” of http://BioRender.com (2021). Taken from https://app.biorender.com/biorender-templates.