Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases

Figure 1

Keap1-Nrf2 signaling. The Keap1 homodimer binds to a single Nrf2 molecule via DLG and ETGE motifs; the latter has a high affinity for Nrf2. Under basal conditions, the Keap1-Nrf2 complex is degraded by Cul3-dependent E3 ubiquitin ligase. However, Keap1 also works as a stress sensor, and oxidative stress induces conformational changes of Keap1-Nrf2 complex. As a result, ubiquitination of Nrf2 is inhibited, and then stabilized Nrf2 is translocated into the nucleus. Binding of Nrf2 with small Maf proteins to the antioxidant response element (ARE) induces many antioxidant and phase II detoxifying enzymes.