Antioxidant defense enzymes and redox pathways

The antioxidant defense enzymes and redox pathways represent a sophisticated network of proteins and small molecules that maintain cellular redox homeostasis by neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) [5, 13]. This system includes primary enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), as well as the thioredoxin and glutathione redox cycles, which are largely coordinated by the master transcription factor Nrf2 [7, 11]. Under physiological conditions, these pathways protect cellular macromolecules from oxidative damage while allowing ROS to function as essential signaling molecules for processes like cell proliferation and immune response [12, 16]. However, chronic imbalance—termed oxidative stress—is a central driver in the pathogenesis of cancer, neurodegenerative disorders, and cardiovascular diseases [1, 10]. Therapeutic interventions aim to either bolster these defenses using Nrf2 activators and enzyme mimetics to prevent tissue damage or, conversely, inhibit them in cancer cells to induce lethal oxidative stress [17, 19]. Despite significant research, clinical success has been limited by the complex, context-dependent roles of redox signaling and the potential for antioxidants to interfere with normal physiological processes or promote drug resistance in tumors [15, 20].

Other names

Endogenous antioxidant systemRedox homeostasis pathwaysCellular antioxidant defense systemAntioxidant defense system

Drugs targeting these pathways act by either inducing the expression of endogenous antioxidant enzymes via the Nrf2-Keap1 axis, mimicking the catalytic activity of enzymes like superoxide dismutase (SOD) or glutathione peroxidase (GPx) to scavenge reactive species, or inhibiting key redox enzymes such as thioredoxin reductase to selectively increase oxidative stress in pathological cells like cancer.