Reactive oxygen species (ROS) generation and antioxidant defense pathways (ROS/Antioxidant pathways)

Reactive oxygen species (ROS) generation and antioxidant defense pathways constitute a complex network responsible for maintaining cellular redox homeostasis (Sies et al., 2017, Nature Reviews Molecular Cell Biology). ROS, including superoxide anions and hydrogen peroxide, are produced primarily as byproducts of mitochondrial respiration or by specialized enzymes such as NADPH oxidases (NOX) (Murphy, 2009, Biochemical Journal). While low levels of ROS serve as critical signaling molecules in processes like cell proliferation and immune defense, excessive accumulation leads to oxidative stress, causing damage to DNA, proteins, and lipids (Schieber & Chandel, 2014, Current Biology). To counteract this, cells employ an antioxidant defense system comprising enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase, which are largely regulated by the Nrf2 transcription factor (Kansanen et al., 2013, Redox Biology). Dysregulation of this balance is a hallmark of numerous pathologies, including cancer, neurodegeneration, and cardiovascular diseases (He et al., 2020, Signal Transduction and Targeted Therapy). Therapeutic strategies focus on either reducing ROS production or enhancing antioxidant capacity to mitigate tissue damage and restore physiological balance. Drugs such as dimethyl fumarate and bardoxolone methyl target these pathways by activating Nrf2 to boost endogenous defenses, while others like N-acetylcysteine act as precursors to essential antioxidants (Liby & Sporn, 2012, Nature Reviews Cancer).

Other names

Redox homeostasisOxidative stress pathwaysROS metabolismAntioxidant systemRedox signaling

Drugs targeting these pathways act by scavenging reactive species, inhibiting ROS-generating enzymes like NADPH oxidase, or activating endogenous antioxidant defenses through the Nrf2-KEAP1 signaling axis (Sies et al., 2017, Nature Reviews Molecular Cell Biology; Liby & Sporn, 2012, Nature Reviews Cancer).