Fig. 2

Schematic illustration of the initiation and roles of the Nrf2-NQO1 pathway in pathological conditions. During conditions of oxidative stress, reactive oxygen/nitrogen species (ROS) react with Kelch-like ECH-associated protein1 (KEAP1), leading to a conformational change that accumulates and releases nuclear factor erythroid 2-related factor 2 (Nrf2), preventing its degradation. Furthermore, small molecules can directly inhibit the Nrf2-KEAP1 interaction, resulting in the liberation of Nrf2. Consequently, Nrf2 translocates into the nucleus and forms heterodimers with small Maf proteins, binding to antioxidant response element enhancer (ARE) sequence and initiating the transcription of antioxidant enzymes, such as NAD(P)H Quinone Dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), and glutathione S-transferase (GST). This triggers the activation of diverse cellular defense mechanisms and initiates the activation of numerous anti-oxidative stress genes. This coordinated response serves as a protective mechanism against cell damage and could be used as a therapeutic approach for various pathologies, including those affecting the central nervous system [1,2,3, 92]