Signalling platforms that modulate the inflammatory response: new targets for drug development.

Christopher A McCulloch, Gregory P Downey, Hani El-Gabalawy

Journal: Nature reviews. Drug discovery 2006;5(10):864-76

PMID: 17016427

Abstract

Therapeutically controlling inflammation is essential for the clinical management of many high-prevalence human diseases. Drugs that block the pro-inflammatory cytokines tumour-necrosis factor-alpha and interleukin-1 (IL-1) can improve outcomes for rheumatoid arthritis and other inflammatory diseases but many patients remain refractory to treatment. Here we explore the need for developing new types of anti-inflammatory drugs and the emergence of novel drug targets based on the clustering of IL-1 receptors into multi-protein aggregates associated with cell adhesions. Interference with receptor aggregation into multi-protein complexes effectively abrogates IL-1 signalling. The exploration of the crucial molecules required for receptor clustering, and therefore signal transduction, offers new targets and scope for anti-inflammatory drug development.

Address: CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Canada M5S 3E2. [email protected]

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