Oxidative stress-related enzymes and redox pathways

The oxidative stress-related enzymes and redox pathways constitute a sophisticated biological network designed to maintain cellular redox homeostasis by balancing the production and neutralization of reactive oxygen species (ROS) [1.1.1, 1.1.2]. Key enzymatic components include superoxide dismutase (SOD), catalase (CAT), and the glutathione peroxidase (GPx) system, which work in concert to detoxify reactive intermediates like superoxide and hydrogen peroxide [1.1.2, 1.3.1]. A master regulator of this network is the Nrf2-Keap1 signaling pathway, which induces the transcription of antioxidant response element (ARE)-containing genes to bolster cellular defenses during stress [1.3.4, 1.5.1]. Dysregulation of these pathways leads to oxidative stress, a state of molecular damage to DNA, lipids, and proteins that drives the progression of chronic conditions such as cancer, neurodegeneration, and cardiovascular disease [1.2.1, 1.3.3]. Pharmacological strategies involve the use of Nrf2 activators, ROS scavengers, and inhibitors of pro-oxidant enzymes like NADPH oxidase (NOX) to restore balance [1.4.1, 1.4.4]. However, therapeutic intervention must be carefully managed to avoid "reductive stress," which can disrupt essential physiological ROS signaling and potentially promote survival in established tumor cells [1.5.1, 1.5.2].

Other names

Antioxidant defense systemRedox signaling pathwaysROS metabolic networkCellular antioxidant enzymesRedox homeostasis pathways

Drugs targeting these pathways primarily work by activating the Nrf2-Keap1 system to induce the expression of endogenous antioxidant genes, directly scavenging reactive oxygen species (ROS), or inhibiting pro-oxidant enzymes such as NADPH oxidase (NOX) and xanthine oxidase [1.3.4, 1.4.1, 1.4.4]. Some agents also act as mimetics of endogenous enzymes like superoxide dismutase (SOD) to accelerate the detoxification of reactive intermediates [1.4.1].