Reactive oxygen species and redox-sensitive inflammatory signaling (ROS/Redox-inflammatory signaling)

Reactive oxygen species (ROS) and redox-sensitive inflammatory signaling describe the integrated biological process where oxidative molecules act as secondary messengers to trigger and amplify inflammatory cascades. ROS, such as superoxide and hydrogen peroxide, modulate the activity of key redox-sensitive transcription factors, most notably Nuclear Factor-kappa B (NF-κB) and Activator Protein-1 (AP-1), which drive the expression of pro-inflammatory cytokines (Morgan & Liu, 2011). This signaling is counterbalanced by the Nrf2-Keap1 pathway, which serves as the primary cellular sensor for oxidative stress and coordinates the antioxidant response (Yamamoto et al., 2018). Chronic dysregulation of this balance leads to a state of persistent oxidative stress and inflammation, which is a hallmark of various pathologies including atherosclerosis, rheumatoid arthritis, and neurodegenerative disorders (Mittal et al., 2014). Therapeutic strategies aimed at this system involve either the direct neutralization of ROS or the pharmacological modulation of redox-sensitive proteins to restore cellular homeostasis. While antioxidants and Nrf2 activators like dimethyl fumarate have shown clinical utility, the ubiquity of ROS in normal physiological processes—such as cell proliferation and host defense—presents a significant challenge for drug development (Sies & Jones, 2020). Consequently, this entry is classified as 'incorrect' as a specific target because it encompasses a broad network of pathways and molecules rather than a single discrete therapeutic target like a specific receptor or enzyme.

Other names

ROS-mediated inflammatory pathwayOxidative stress-induced signalingRedox-inflammatory axisROS-NF-kappaB signaling pathway

Drugs targeting this system typically act by scavenging reactive oxygen species (ROS), inhibiting ROS-generating enzymes like NADPH oxidase (NOX), or activating the Nrf2-Keap1 antioxidant response element (ARE) pathway to enhance endogenous antioxidant defenses and suppress pro-inflammatory transcription factors like NF-κB.