Nuclear factor kappa-light-chain-enhancer of activated B cells inflammatory pathway (NF-κB pathway)

The NF-κB inflammatory pathway is a complex intracellular signaling cascade that integrates extracellular inflammatory and stress signals to regulate transcription of genes critical for immune responses, inflammation, cell survival, and proliferation[1][2][3][4][5][6]. Canonical NF-κB signaling is rapidly activated by acute inflammatory stimuli, while the noncanonical pathway responds to chronic immune signals. Dysfunction or constitutive activation of this pathway drives the pathology of many inflammatory, autoimmune, and neoplastic diseases, making it a major therapeutic target. Drugs that modulate the pathway target components like the IκB kinase complex, NF-κB nuclear translocation, DNA binding, and upstream cytokine signaling[4][6]. However, comprehensive targeting presents significant safety and selectivity challenges due to the pathway's broad physiological roles[6].

Other names

NF-κB signaling pathwayNuclear factor kappa-light-chain-enhancer of activated B cells pathwayCanonical NF-κB pathwayClassical NF-κB pathwayNoncanonical NF-κB pathway (alternative form involving IKKα/NIK)

Inhibition of IKK kinase activity to prevent IκB phosphorylation/degradation; Stabilization of IκB to sequester NF-κB in the cytoplasm; Blocking NF-κB nuclear translocation or DNA binding; Modulation of upstream cytokine signaling (IL-1, TNF-α); Inhibition of proteasomal degradation of pathway components; Interference with post-translational modifications (ubiquitination, phosphorylation, acetylation) of NF-κB subunits