Title: MD-2 (Myeloid differentiation 2) as Drug Target
Abstract: Microbial lipopolysaccharide (LPS) is an endotoxin conveying to the surface receptor complex of toll-like receptor 4 (TLR4)-myeloid differentiation 2 (MD-2) in the innate immune cells through ancillary proteins such as LPS-binding protein and CD14. However, TLR4 alone is not sufficient for the recognition of LPS. MD-2 is absolutely required for sensing the lipid A domain of LPS and for triggering LPS-induced TLR4 activity across the plasma membrane. Thereby, lipid A domain and its binding to MD-2 are potential drug targets to intervene endotoxemia as well as other disorders associated with LPS etiology. Here, we reviewed MD-2 as drug target focused on drug candidates-targeting TLRs, transport of microbial LPS into TLR4/MD-2, crystal structure of TLR4/MD-2 alone, crystal structure of TLR4/MD-2 with bound LPS, lipid A derivatives as MD-2 antagonist, non-lipid antagonists of LPS binding to MD-2, and human disorders-implicated with TLR4/MD-2. This review could be helpful to understand the TLR4/MD-2 biology and suggests that MD-2 is an important therapeutic target against inflammatory diseases due to infection.
Publication Year: 2010
Publication Date: 2010-06-01
Language: en
Type: article
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