Regulation of Keap1-Nrf2 signaling in health and diseases.

Nuclear factor erythroid 2-related factor 2 (Nrf2) functions as a central regulator in modulating the activities of diverse antioxidant enzymes, maintaining cellular redox balance, and responding to oxidative stress (OS). Kelch-like ECH-associated protein 1 (Keap1) serves as a principal negative modulator in controlling the expression of detoxification and antioxidant genes. It is widely accepted that OS plays a pivotal role in the pathogenesis of various diseases. When OS occurs, leading to inflammatory infiltration of neutrophils, increased secretion of proteases, and the generation of large quantities of reactive oxygen radicals (ROS). These ROS can oxidize or disrupt DNA, lipids, and proteins either directly or indirectly. They also cause gene mutations, lipid peroxidation, and protein denaturation, all of which can result in disease. The Keap1-Nrf2 signaling pathway regulates the balance between oxidants and antioxidants in vivo, maintains the stability of the intracellular environment, and promotes cell growth and repair. However, the antioxidant properties of the Keap1-Nrf2 signaling pathway are reduced in disease. This review overviews the mechanisms of OS generation, the biological properties of Keap1-Nrf2, and the regulatory role of its pathway in health and disease, to explore therapeutic strategies for the Keap1-Nrf2 signaling pathway in different diseases.