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

Oxidative stress and reactive oxygen species (ROS)–related pathways encompass the complex biochemical processes involved in the generation, signaling, and detoxification of oxygen-derived free radicals and non-radical oxidants [1]. ROS, such as superoxide and hydrogen peroxide, serve as critical secondary messengers in physiological signal transduction, regulating cell growth, differentiation, and immune responses [2]. However, an imbalance between ROS production and antioxidant defense mechanisms leads to oxidative damage of lipids, proteins, and DNA, which is a hallmark of the pathophysiology of cancer, neurodegeneration, and cardiovascular diseases [4][5]. Therapeutic interventions targeting these pathways aim to restore redox homeostasis through the use of direct scavengers or by modulating regulatory proteins like Nrf2 to enhance the cell's natural antioxidant capacity [3]. Despite their potential, targeting these pathways is challenging due to the dual role of ROS in both health and disease, where excessive suppression can disrupt essential cellular functions and lead to unintended side effects [5]. (Citations: [1] Sies & Jones, 2020, Nat Rev Mol Cell Biol; [2] Pizzino et al., 2017, Oxid Med Cell Longev; [3] He et al., 2020, Trends Pharmacol Sci; [4] National Cancer Institute Dictionary; [5] Forman & Zhang, 2021, Nat Rev Drug Discov).

Other names

Redox signaling pathwaysOxidative stress responseReactive oxygen species metabolismAntioxidant defense systemROS-mediated signaling

Drugs targeting these pathways typically act by directly scavenging reactive species, inhibiting ROS-generating enzymes such as NADPH oxidase (NOX), or activating cytoprotective transcription factors like Nuclear factor erythroid 2-related factor 2 (Nrf2) to upregulate endogenous antioxidant enzymes [3][5].