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KMID : 1004820100110020093
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Journal of Biomedical Research
2010 Volume.11 No. 2 p.93 ~ p.102
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MD-2 (Myeloid differentiation 2) as Drug Target
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Jung Sang-Hun
Han Sang-Bae
Kim Young-Soo
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Abstract
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Microbial lipopolysaccharide (LPS) is an endotoxin conveying the surface receptor complex of toll-like receptor 4 (TLR4)-myeloid differentiation 2 (MD-2) in innate immune cells through ancillary proteins such as LPS-binding protein and CD14. However, TLR4 alone is not sufficient for recognition of LPS. MD-2 is essential for sensing the lipid A domain of LPS and for triggering LPS-induced TLR4 activity across the plasma membrane. Therefore, lipid A domain and its binding to MD-2 are potential drug targets for intervention in endotoxemia as well as other disorders associated with LPS etiology. Here, we reviewed MD-2 as a 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 understanding the biology of TLR4/MD-2, and suggests the importance of MD-2 as a therapeutic target against inflammatory diseases due to infection.
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KEYWORD
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Endotoxin LPS, TLR4, MD-2, Eritoran, Non-lipid LPS antagonist
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