Reactive oxygen species regulation and endogenous antioxidant pathways (ROS/Antioxidant Pathways)

Reactive oxygen species (ROS) regulation and endogenous antioxidant pathways represent the integrated cellular systems responsible for maintaining redox homeostasis. This complex network includes enzymatic antioxidants such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), which neutralize superoxide radicals and hydrogen peroxide (Sies & Jones, 2020, Nature Reviews Molecular Cell Biology). The master regulator of this system is the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), which, upon activation, translocates to the nucleus to induce the expression of a battery of cytoprotective and antioxidant genes (Yamamoto et al., 2018, Physiological Reviews). While ROS are essential at low levels for physiological signaling, their chronic overproduction leads to oxidative stress, causing cumulative damage to DNA, proteins, and lipids. This oxidative damage is a primary driver in the pathogenesis of cancer, neurodegeneration (such as Alzheimer's and Parkinson's), and cardiovascular diseases (Formigari et al., 2007, Free Radical Biology and Medicine). Pharmacological strategies targeting these pathways typically focus on Nrf2 activators like dimethyl fumarate or the administration of glutathione precursors like N-acetylcysteine to bolster cellular defenses (Liby & Sporn, 2012, Pharmacological Reviews). However, therapeutic development is challenged by the need to selectively target pathological oxidative stress without disrupting the vital roles ROS play in immune function and normal cell signaling.

Other names

Redox homeostasisAntioxidant defense systemOxidative stress response pathwayCellular redox regulation

Activation of the Nrf2-Keap1 signaling pathway to induce antioxidant response element (ARE)-driven genes; direct scavenging of free radicals; replenishment of intracellular glutathione pools; and enzymatic neutralization of superoxide and hydrogen peroxide.