Endogenous antioxidant defense system

The endogenous antioxidant defense system is a complex biological network of enzymes and non-enzymatic molecules that maintain cellular redox homeostasis by neutralizing reactive oxygen and nitrogen species (ROS/RNS) (Halliwell & Gutteridge, 2015). Primary enzymatic components include superoxide dismutase (SOD), catalase, and glutathione peroxidase, which work in concert with non-enzymatic antioxidants like glutathione (GSH) and uric acid (Birben et al., 2012). The system is primarily regulated by the transcription factor Nrf2, which coordinates the expression of genes containing antioxidant response elements (ARE) (Kansanen et al., 2013). Dysregulation of this system leads to oxidative stress, a key driver in the progression of neurodegenerative diseases, cardiovascular disorders, and cancer (Sies, 2015). Pharmacological interventions, such as Nrf2 activators (e.g., dimethyl fumarate) or glutathione precursors (e.g., N-acetylcysteine), aim to enhance these defenses to mitigate tissue damage (Cuadrado et al., 2019). However, therapeutic targeting is complex, as excessive antioxidant activity can lead to reductive stress or inadvertently protect malignant cells from oxidative damage (Gutteridge & Halliwell, 2010).

Other names

Antioxidant defense systemCellular antioxidant systemEndogenous antioxidant network

Activation of the Nrf2-Keap1 signaling pathway to induce antioxidant gene expression, replenishment of intracellular glutathione levels, and direct enzymatic neutralization of superoxide and hydrogen peroxide (Kansanen et al., 2013; Birben et al., 2012).