Oxidative stress pathways and reactive oxygen species (ROS) (ROS)

Oxidative stress is a physiological state characterized by an imbalance between the generation of reactive oxygen species (ROS) and the capacity of antioxidant defense mechanisms to neutralize them [Pizzino et al., 2017, Oxidative Medicine and Cellular Longevity]. ROS, such as superoxide, hydrogen peroxide, and hydroxyl radicals, are produced during mitochondrial respiration and by enzymes like NADPH oxidases, serving as critical secondary messengers in signal transduction at low concentrations [Sies et al., 2017, Nature Reviews Molecular Cell Biology]. However, chronic elevation of ROS leads to oxidative damage of cellular macromolecules, including DNA, lipids, and proteins, which is a hallmark of aging and various chronic diseases like cancer, diabetes, and neurodegeneration [He et al., 2020, Signal Transduction and Targeted Therapy]. Pharmacological intervention aims to restore redox balance through the use of antioxidants or by modulating pathways like Nrf2 that upregulate protective enzymes [StatPearls, 2023]. Because ROS are also essential for normal cellular functions like pathogen defense and cell signaling, therapeutic targeting requires precise modulation to avoid detrimental side effects such as the disruption of essential physiological processes [Journal of Clinical Investigation, 2018].

Other names

Redox signalingOxidative damageAntioxidant defense systemROS-mediated signaling

Drugs targeting these pathways typically act by directly scavenging reactive species, inhibiting ROS-generating enzymes like NADPH oxidase, or activating endogenous antioxidant response pathways, most notably the Nrf2-KEAP1 system [He et al., 2020, Signal Transduction and Targeted Therapy].