Cellular antioxidant defense pathways

The cellular antioxidant defense pathways comprise a complex network of enzymatic and non-enzymatic systems designed to maintain redox homeostasis and protect cells from oxidative damage caused by reactive oxygen species (ROS) [NIH, 1.3.2]. Key enzymatic components include superoxide dismutase (SOD), catalase, and glutathione peroxidase, while non-enzymatic defenses involve molecules like glutathione and vitamins C and E [Wikipedia, 1.3.4]. The master regulator of this system is the Nrf2-Keap1 pathway, which coordinates the transcriptional induction of numerous antioxidant and detoxification genes in response to oxidative stress [PubMed, 1.1.3]. Dysregulation of these pathways is implicated in a wide range of pathologies, including neurodegenerative diseases, cardiovascular disorders, and cancer, where oxidative stress drives tissue damage or promotes tumor progression [NIH, 1.3.1]. Therapeutic strategies often focus on activating these pathways to enhance cellular resilience or, conversely, inhibiting them in cancer cells to overcome chemoresistance [MDPI, 1.2.4]. Drugs such as dimethyl fumarate and various Nrf2 activators are used or being investigated to modulate these pathways for clinical benefit [PubMed, 1.1.3].

Other names

Antioxidant defense systemEndogenous antioxidant systemRedox homeostasis pathwaysAntioxidant response element (ARE) pathway

Activation of the Nrf2-ARE signaling pathway to induce expression of antioxidant and detoxification enzymes; direct scavenging of reactive oxygen species (ROS); restoration of glutathione levels.