Oxidative stress and antioxidant defense pathway (OS/ADP)

The oxidative stress and antioxidant defense pathway is a fundamental biological system responsible for maintaining the balance between the production of reactive oxygen species (ROS) and the cellular mechanisms that neutralize them. ROS, such as superoxide and hydrogen peroxide, are natural byproducts of aerobic metabolism and serve as essential signaling molecules at low concentrations; however, excessive accumulation leads to oxidative damage to DNA, proteins, and lipids (Sies et al., 2017, Nature Reviews Molecular Cell Biology). The defense system comprises enzymatic antioxidants like superoxide dismutase (SOD), catalase, and glutathione peroxidase, alongside non-enzymatic molecules like glutathione and vitamins C and E (He et al., 2020, Signal Transduction and Targeted Therapy). A central regulator of this pathway is the Nrf2-Keap1 system, which coordinates the expression of numerous cytoprotective genes in response to oxidative challenge (Hayes & Dinkova-Kostova, 2014, Trends in Biochemical Sciences). Chronic oxidative stress is implicated in the pathogenesis of diverse conditions, including neurodegeneration, cardiovascular disease, and chronic inflammation. Therapeutic strategies targeting this pathway include Nrf2 activators, which enhance endogenous defenses, and direct-acting antioxidants, though clinical success has been mixed due to the complexity of redox signaling (Forman & Zhang, 2021, Free Radical Biology and Medicine).

Other names

Redox signaling pathwayAntioxidant response element (ARE) pathwayNrf2-Keap1 signaling pathwayReactive oxygen species (ROS) management systemCellular redox homeostasis

Drugs targeting these pathways typically act by directly scavenging reactive oxygen species (ROS), chelating transition metals to prevent hydroxyl radical formation, or activating endogenous antioxidant defenses, most notably through the Nrf2-Keap1-ARE signaling axis to induce the expression of phase II detoxifying enzymes and antioxidant proteins (He et al., 2020, Signal Transduction and Targeted Therapy).