Diverse agents act at multiple levels to inhibit the Rel/NF-kappaB signal transduction pathway

Rel/NF-kappaB transcription factors regulate several important physiological processes, including developmental processes, inflammation and immune responses, cell growth, cancer, apoptosis, and the expression of certain viral genes. Therefore, they have also been sought-after molecular targets for pharmacological intervention. As details of the Rel/NF-kappaB signal transduction pathway are revealed, it is clear that modulators of this pathway can act at several levels. Inhibitors of the Rel/NF-kappaB pathway include a variety of natural and designed molecules, including anti-oxidants, proteasome inhibitors, peptides, small molecules, and dominant-negative or constitutively active polypeptides in the pathway. Several of these molecules act as general inhibitors of Rel/NF-kappaB induction, whereas others inhibit specific pathways of induction. Inhibitors of Rel/NF-kappaB are likely to gain stature as treatments for certain cancers and neurodegenerative and inflammatory diseases.