Proteins and other macromolecules involved in oxidative stress pathways

Proteins and other macromolecules involved in oxidative stress pathways constitute a diverse regulatory network essential for maintaining cellular redox homeostasis. This system includes reactive oxygen species (ROS)-generating enzymes such as NADPH oxidase (NOX) and xanthine oxidase, as well as an intricate antioxidant defense system comprising enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase [Wikipedia; Frontiers in Oncology, 2024]. A central regulator of this pathway is the transcription factor Nrf2, which, upon dissociation from its negative regulator Keap1, translocates to the nucleus to induce the expression of numerous cytoprotective and antioxidant genes [NIH, 2025; MDPI, 2020]. Chronic imbalance between ROS production and antioxidant capacity leads to oxidative stress, causing damage to lipids, proteins, and DNA, which is a hallmark of diseases such as cancer, neurodegeneration, and atherosclerosis [MDPI, 2024; NIH, 2022]. Therapeutic interventions often target these pathways using Nrf2 activators like dimethyl fumarate, ROS scavengers such as N-acetylcysteine, or enzyme inhibitors like allopurinol to restore redox balance [MDPI, 2025; Frontiers, 2025]. However, because low levels of ROS serve as vital signaling molecules, a state known as eustress, therapeutic modulation must be carefully calibrated to avoid disrupting essential physiological processes [MDPI, 2020]. Furthermore, the overactivation of antioxidant pathways in certain contexts, such as established tumors, can promote cancer cell survival and resistance to chemotherapy [NIH, 2025]. Consequently, these pathways represent both a significant therapeutic opportunity and a complex challenge in precision medicine.

Other names

Redox signaling componentsAntioxidant defense systemPro-oxidant enzymesROS/RNS regulatory networkOxidative stress pathway

Mechanisms include the activation of the Nrf2/ARE pathway to induce antioxidant enzymes, direct scavenging of reactive oxygen species (ROS), inhibition of ROS-generating enzymes like NADPH oxidase (NOX) and xanthine oxidase (XO), and modulation of redox-sensitive signaling cascades such as NF-κB and MAPK [Frontiers in Oncology, 2024; MDPI, 2020].