05 Nov 1998

It is known that aspirin and sodium salicylate suppress inflammation by inhibiting cyclooxygenase, an enzyme that triggers production of prostaglandin. It has been suspected that these compounds also exert their anti-inflammatory effects through a second pathway, involving activation of NF-KB, a family of cellular transcription factors involved in the inducible expression of genes regulating the immune response. In today's Nature, Richard B. Gaynor and colleagues from the University of Texas Southwestern Medical Center, confirm that aspirin and salicylate bind directly to the cellular kinase IKK-β, blocking ATP binding and the subsequent activation of NF-KB genes. This work raises the possibility of designing a new class of drugs to inhibit the inflammatory response without the undesirable side effects of aspirin. Such drugs may help dampen inflammation in the brain, which is thought to contribute to the pathogenesis of Alzheimer's disease.—June Kinoshita