Reactive oxygen species and associated redox pathways (ROS)

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules, including free radicals like superoxide and non-radicals like hydrogen peroxide, that serve as critical signaling molecules in physiological processes such as cell growth and immune defense [Schieber & Chandel, 2014]. Under normal conditions, these species are tightly regulated by endogenous antioxidant systems to maintain cellular homeostasis. However, an imbalance between ROS production and the cell's antioxidant capacity leads to oxidative stress, which causes cumulative damage to DNA, proteins, and lipids [Pizzino et al., 2017]. This oxidative damage is a primary driver in the pathogenesis of various conditions, including cancer, neurodegeneration, and cardiovascular diseases. Therapeutic intervention in these pathways involves either direct neutralization of ROS using scavengers or the modulation of redox-sensitive enzymes and transcription factors, most notably the Nrf2-KEAP1 system which regulates the expression of numerous antioxidant genes [Zhang et al., 2013]. Additionally, targeting ROS-generating enzymes like NADPH oxidases (NOX) has emerged as a strategy to prevent excessive ROS production at the source. Despite the clear link between ROS and disease, clinical success has been limited by the complexity of redox biology, where complete suppression of ROS can interfere with vital cellular functions [Sies, 2015]. Future therapeutic efforts are focused on achieving site-specific and context-dependent modulation of redox signaling to avoid the pitfalls of systemic antioxidant therapy.

Other names

Oxidative stress pathwaysRedox signalingOxygen radicalsReactive oxygen intermediatesPro-oxidants

Drugs targeting these pathways act through direct scavenging of free radicals, inhibition of ROS-generating enzymes like NADPH oxidase (NOX) and xanthine oxidase, or by inducing endogenous antioxidant defenses via the activation of the Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway [Sies et al., 2017; Pizzino et al., 2017].