Redox-sensitive signaling pathway (RSSP)

Redox-sensitive signaling pathways involve the regulation of cellular processes through the modification of signaling molecules by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In inflammatory contexts, elevated ROS levels act as secondary messengers that activate key transcription factors, such as Nuclear Factor-kappa B (NF-kappaB) and Activator Protein-1 (AP-1), leading to the robust production of pro-inflammatory cytokines like TNF-alpha, IL-6, and IL-1beta (Gloire et al., 2006; Morgan & Liu, 2011). This activation often occurs through the oxidative modification of critical cysteine residues on upstream kinases, such as the IKK complex, or the inactivation of phosphatases that normally restrain inflammatory signaling (Marinho et al., 2014). Chronic activation of these pathways is a central driver in the pathogenesis of various conditions, including cardiovascular diseases, neurodegeneration, and chronic obstructive pulmonary disease (Mittal et al., 2014). Therapeutic interventions targeting this system include direct antioxidants, NADPH oxidase (NOX) inhibitors, and Nrf2 activators like dimethyl fumarate, which bolster the cell's natural antioxidant defenses to suppress cytokine production (He et al., 2020). However, targeting these pathways is challenging due to the dual role of ROS in both pathological signaling and essential physiological processes like host defense and cell differentiation (Sies & Jones, 2020).

Other names

Redox signalingROS-mediated inflammatory pathwayOxidative stress-induced signalingRedox-regulated cytokine production

Modulation of cellular redox potential, inhibition of ROS-generating enzymes (e.g., NADPH oxidase), and activation of antioxidant response elements (ARE) via Nrf2 to suppress pro-inflammatory transcription factor activity.