NF-κB : A Future Drug Target

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a transcription factor that started its life as a B cell-specific nuclear protein, but has matured to become one of the most extensively studied transcriptional regulators, found to control many pathophysiological processes. Its role ranges from its transcriptional regulatory functions to its participation in diverse processes, including inflammation, immunity, mucosal homeostasis and cancer. NF-kB regulates the expression of over 200 genes that are involved in a variety of functions. It is basically a protein complex found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.

NF-κB plays a key role in regulating the immune response to infection. It regulates the expression of cytokines, inducible nitric oxide synthase (iNOS), cyclo-oxgenase 2 (COX-2), growth factors, inhibitors of apoptosis and effector enzymes in response to ligation of many receptors involved in immunity including T-cell receptors (TCRs), B-cell receptors (BCRs) and members of the Toll-like receptor/IL-1 receptor super family. It also takes part in the development and the activity of a number of tissues including the central nervous system. Moreover, pathological dysregulation of NF-κB is linked to inflammatory and autoimmune diseases as well as cancer. Activation of the NF-κB/Rel transcription family, by nuclear translocation of cytoplasmic complexes, plays a central role in inflammation through its ability to induce transcription of proinflammatory genes. This pathway is activated upon appropriate cellular stimulation, most often by signals related to pathogens or stress.

In the below link, we will discuss the the regulation of NF-κB activity by IκB proteins and IκB kinase (IKK), specificity of various NF-κB proteins, their role in inflammatory disease, and the development of therapeutic strategies aimed at inhibition of NF-κB.

NF-κB A Future Drug Target.pdf