Antioxidant redox network

The antioxidant redox network is a sophisticated, multi-layered system of enzymes and small molecules that maintains cellular redox homeostasis by regulating the production and elimination of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [1]. This network includes primary antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), as well as non-enzymatic components like glutathione (GSH), thioredoxin, and dietary antioxidants like vitamins C and E [2]. The network is centrally regulated by the Nrf2 (Nuclear factor erythroid 2-related factor 2) signaling pathway, which orchestrates the expression of numerous cytoprotective genes in response to oxidative stress [3]. Dysregulation of this network is a hallmark of many chronic conditions, including cancer, neurodegenerative diseases (like Parkinson's and Alzheimer's), and cardiovascular disorders, where excessive ROS lead to macromolecular damage [4]. Therapeutic strategies often focus on specific nodes within the network, such as Nrf2 activators (e.g., dimethyl fumarate) or glutathione precursors (e.g., N-acetylcysteine), to bolster the cell's natural defenses [5]. However, targeting the network is challenging because ROS also function as essential signaling molecules for cell growth and immune responses; thus, excessive antioxidant intervention can lead to "reductive stress" and unintended toxicity [6]. [1] Sies, H., et al. (2017). Nature Reviews Molecular Cell Biology. [2] Halliwell, B., & Gutteridge, J. M. (2015). Free Radicals in Biology and Medicine. [3] Ma, Q. (2013). Annual Review of Pharmacology and Toxicology. [4] Forman, H. J., & Zhang, H. (2021). Nature Reviews Drug Discovery. [5] Liby, K. T., & Sporn, M. B. (2012). Nature Reviews Cancer. [6] Ursini, F., et al. (2016). Redox Biology.

Other names

Redox systemAntioxidant defense systemCellular redox homeostasisRedoxome

Activation of the Nrf2-Keap1 pathway to induce cytoprotective genes, direct scavenging of reactive oxygen species (ROS), and replenishment of endogenous antioxidant pools such as glutathione.