Oxidative stress and antioxidant defense pathways

Oxidative stress and antioxidant defense pathways constitute the cellular machinery responsible for maintaining redox homeostasis by balancing the production of reactive oxygen species (ROS) with their neutralization. Under physiological conditions, ROS serve as important signaling molecules; however, an imbalance—termed oxidative stress—leads to oxidative damage of DNA, proteins, and lipids, contributing to the pathogenesis of chronic diseases such as Alzheimer's, atherosclerosis, and diabetes (Source: NIH, PubMed). The central regulator of the antioxidant response is the transcription factor Nrf2, which, upon activation, translocates to the nucleus to induce the expression of protective enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx) (Source: UniProt). Pharmacological intervention in these pathways typically involves either the use of direct antioxidants to scavenge ROS or the development of Nrf2 activators to bolster endogenous defense mechanisms. While promising for treating inflammatory and degenerative conditions, therapeutic targeting must be carefully calibrated to avoid disrupting essential redox-sensitive signaling pathways or inadvertently supporting the survival of malignant cells (Source: Nature Reviews Drug Discovery). Additionally, biomarkers such as malondialdehyde and 8-hydroxy-2-deoxyguanosine are frequently used to monitor the efficacy of these interventions in clinical settings (Source: PubMed).

Other names

Redox signaling pathwaysAntioxidant response systemROS scavenging pathwaysCellular redox homeostasis

Activation of the Nrf2-ARE signaling pathway to induce endogenous antioxidant enzymes, direct scavenging of reactive oxygen species, and replenishment of cellular thiol pools such as glutathione.