Intracellular glutathione and Nuclear factor kappa B pathway components (GSH/NF-κB)

Intracellular glutathione (GSH) and the Nuclear factor kappa B (NF-κB) pathway components constitute a fundamental regulatory network that integrates cellular redox homeostasis with the inflammatory response. Glutathione is a tripeptide antioxidant (L-gamma-glutamyl-L-cysteinyl-glycine) that protects cells from oxidative damage by neutralizing reactive oxygen species (ROS) and acting as a cofactor for various enzymes (PubChem, CID 124886). The NF-κB pathway consists of a family of inducible transcription factors, such as p65 (RelA) and p50, which are sequestered in the cytoplasm by IκB inhibitory proteins until activated by stimuli like cytokines or oxidative stress (PubMed, PMID: 10713350). Depletion of intracellular GSH often leads to an increase in ROS, which can trigger the IKK-mediated phosphorylation and degradation of IκB, allowing NF-κB to translocate to the nucleus and initiate the transcription of pro-inflammatory and pro-survival genes (PubMed, PMID: 15496446). This axis is frequently dysregulated in chronic inflammatory conditions, neurodegenerative diseases, and malignancies, where persistent NF-κB activation and oxidative stress drive disease progression (PubMed, PMID: 21233414). Pharmacological agents like N-acetylcysteine (NAC) or dimethyl fumarate target this system by replenishing GSH pools or inhibiting NF-κB signaling to mitigate tissue damage and inflammation (PubMed, PMID: 24835770).

Other names

GSH and NF-kappaBRedox-regulated signaling componentsGlutathione-NF-kappaB axisGSH/NF-kB pathway

Modulation of cellular redox state through glutathione replenishment and inhibition of the IKK/NF-κB signaling cascade to suppress pro-inflammatory gene expression.