Reactive oxygen species and reactive nitrogen species redox pathways (ROS/RNS pathways)

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive molecules, including superoxide, hydrogen peroxide, and nitric oxide, that serve as critical signaling mediators in cellular redox pathways (Sies et al., 2017, Nature Reviews Molecular Cell Biology). Under physiological conditions, these species regulate essential processes such as vascular tone, immune response, and gene expression through the reversible oxidation of protein thiols (Forman & Zhang, 2021, Nature Reviews Drug Discovery). However, an imbalance between the production of ROS/RNS and the capacity of antioxidant defense systems leads to oxidative and nitrosative stress, resulting in damage to DNA, proteins, and lipids (NIH, National Cancer Institute). This damage is a key driver in the pathogenesis of various conditions, including cancer, neurodegenerative diseases, and cardiovascular disorders (PubMed, PMID: 28853155). Therapeutic strategies targeting these pathways aim to restore redox homeostasis by using direct scavengers, inhibiting ROS-producing enzymes like NADPH oxidase, or activating transcription factors such as Nrf2 to enhance endogenous antioxidant defenses (StatPearls, "Antioxidants"). Despite their potential, drug development faces challenges due to the "redox paradox," where non-selective suppression of these species can interfere with vital signaling, potentially leading to toxicity or "reductive stress" (Wikipedia, "Oxidative stress").

Other names

Oxidative stress pathwaysRedox signalingReactive oxygen and nitrogen speciesRONSRedox homeostasis

Pharmacological agents modulate these pathways by directly scavenging reactive species, inhibiting ROS-generating enzymes such as NADPH oxidase (NOX) and xanthine oxidase, or activating the Nrf2-Keap1 signaling axis to induce the expression of endogenous antioxidant enzymes like superoxide dismutase and glutathione peroxidase.