Target Analysis - Toll-like receptors
The role of Toll-like receptors as a target for therapeutics
Introduction to Toll-like receptors
It is well-established that the innate immune system is essential to human survival, providing the first line of defence by recognizing and responding to pathogenic threats when microorganisms breach the body's barriers. For many years, the signalling pathways involved in this system were unknown, but recent work using positional cloning and knockout animal models has provided us with knowledge of some of the most powerful receptors involved in innate immunity - the Toll-like receptors (TLRs).
With the discovery of endogenous ligands for TLRs and other pattern recognition receptors (PRPs), it has become increasingly evident that TLRs may not only be involved in recognizing the threat from invading pathogens, but also in sensing tissue damage due to disease or injury as well as having a key role in initiating cellular repair mechanisms.
A greater understanding of the immune system holds huge potential for the development of therapeutics for bacterial and viral infections, allergies and cancer, and also to limit the damage caused by autoimmune disorders. Aditionally, the role of TLRs in tissue repair and regeneration provides a further avenue for drug targeting. However, developing therapeutics based on manipulation of Toll signalling is not straightforward. The fine balance of cell signalling these receptors participate in has wide-ranging and powerful effects on gene expression affecting thousands of individual genes; clearly, the issue of side-effects could be quite an obstacle.
