Cellular antioxidant defense pathways and reactive oxygen species (ROS/Antioxidant pathways)

Cellular antioxidant defense pathways comprise a complex network of enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, along with non-enzymatic molecules like glutathione that work in concert to neutralize reactive oxygen species (ROS) [1][2]. While ROS are essential byproducts of aerobic metabolism and serve as critical signaling molecules at low concentrations, their excessive accumulation leads to oxidative stress, which causes damage to DNA, lipids, and proteins [2]. This imbalance is a primary driver in the pathogenesis of various conditions, including cancer, neurodegenerative disorders like Alzheimer's, and cardiovascular diseases [4]. Therapeutic interventions typically aim to bolster these defenses by activating master regulators like the Nuclear factor erythroid 2-related factor 2 (Nrf2) or by providing exogenous antioxidants to restore redox balance [3]. However, targeting these pathways is clinically challenging because complete suppression of ROS can interfere with vital cellular processes, potentially leading to 'reductive stress' or inadvertently promoting the survival of malignant cells [2][5]. Sources: [1] NIH/NCBI: "Antioxidant Defense Systems" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724665/) [2] Nature Reviews Molecular Cell Biology: "Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling" (https://www.nature.com/articles/nrm3918) [3] Frontiers in Pharmacology: "The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress" (https://www.frontiersin.org/articles/10.3389/fphar.2016.00060/full) [4] StatPearls: "Antioxidants" (https://www.ncbi.nlm.nih.gov/books/NBK541064/) [5] PubMed: "Reductive stress: an emerging concept in health and disease" (https://pubmed.ncbi.nlm.nih.gov/32128215/)

Other names

Redox homeostasis systemAntioxidant response element (ARE) pathwayOxidative stress defense systemEndogenous antioxidant system

Activation of the Nrf2 transcription factor to induce antioxidant response element (ARE)-mediated gene expression; direct scavenging of reactive oxygen species; replenishment of glutathione stores; mimetic activity of antioxidant enzymes like superoxide dismutase or glutathione peroxidase [1][3].