The nuclear factor-kappaB (NF-κB): from a versatile transcription factor to a ubiquitous therapeutic target

The nuclear factor-kappaB (NF-κB) transcription factors regulate a plethora of cellular pathways and processes including the immune response, inflammation, proliferation, apoptosis and calcium homeostasis. In addition to the complexity of its physiological roles, the composition and function of this family of proteins is very complicated. While the basic understanding of NF-κB signalling is extensive, relatively little is know of the in vivo dynamics of this pathway or what controls the balance between various outcomes. Although we know a large number of NF-κB-responsive genes, the contribution of these genes to a specific response is not always clear. Finally, the involvement of NF-κB in pathological processes is only now beginning to be unravelled. In addition to cancer and immunodeficiency disorders, altered regulation of NF-κB has been associated with several inherited diseases. These findings indicate that modulation of the NF-κB pathways may be beneficial. However, our limited knowledge of NF-κB signalling hinders therapeutic approaches: in many situations it is not clear whether the enhancement or inhibition of NF-κB activity would be beneficial or which pathways to interfere with and what the required level of activation is. Further studies of the role of NF-κB are needed as these may result in novel therapeutic strategies for a wide variety of diseases