Adaptors in toll-like receptor signaling and their potential as therapeutic targets.

Abstract:

: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.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Ve T,Gay NJ,Mansell A,Kobe B,Kellie S

doi

10.2174/138945012803530260

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

1360-74

issue

11

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-20120528-21

journal_volume

13

pub_type

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