Endogenous antioxidant defense pathways

The endogenous antioxidant defense pathways represent a sophisticated biological network responsible for maintaining cellular redox balance and protecting against oxidative damage. This system includes primary antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), which neutralize reactive oxygen species (ROS) like superoxide and hydrogen peroxide (Ighodaro & Akinloye, 2018, Alexandria Journal of Medicine). A central regulator of this system is the Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that, upon activation, translocates to the nucleus to bind the antioxidant response element (ARE) and induce the expression of numerous cytoprotective genes (He et al., 2020, Frontiers in Pharmacology). Dysregulation of these pathways is a hallmark of various conditions, including neurodegenerative diseases, cardiovascular disorders, and chronic inflammation, where excessive ROS production overwhelms the innate defense capacity (Forman & Zhang, 2021, Free Radical Biology and Medicine). Therapeutic strategies often focus on Nrf2 activators, such as dimethyl fumarate, or antioxidant mimetics to restore redox homeostasis (Robledinos-Antón et al., 2019, Antioxidants). However, pharmacological intervention must be carefully managed to avoid the "Nrf2 paradox," where over-activation may inadvertently support the survival and chemoresistance of malignant cells.

Other names

Antioxidant defense systemEndogenous antioxidant systemCellular redox regulatory networkAntioxidant response element (ARE) pathway

Activation of the Nrf2-Keap1-ARE signaling axis to upregulate the transcription of cytoprotective and antioxidant enzymes, alongside direct scavenging of reactive oxygen species by antioxidant mimetics.