To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins
through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include
MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually
considered a part of the TIR domain-containing adaptor protein group. Other TIR domain-containing proteins have
also been shown to regulate these signaling pathways, including ST2 and SIGIRR, as well as several bacterial and viral
TIR domain-containing proteins that modulate these pathways as virulence factors. TLR pathways and the adaptor proteins
are associated with a number of diseases, including infection, sepsis, inflammatory, allergic and autoimmune diseases
and cancer. We review our current understanding of the structure and function of adaptor proteins and their regulatory
proteins, their association with disease and their potential as therapeutic targets in human disease.
Keywords: Toll-like receptors (TLRs), TIR (Toll/interleukin-1 receptor) domain, adaptor proteins, Therapeutic Targets, signaling adaptor proteins, PAMPs, ligand-receptor interaction, ST2, SIGIRR, signaling pathways.
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