Abstract
Toll-like receptors are an integral part of innate immunity in the central nervous system (CNS); they orchestrate a robust defense in response to both exogenous and endogenous danger signals. Recently, toll-like receptor 4 (TLR4) has emerged as a therapeutic target for the treatment of CNS-related diseases such as sepsis and chronic pain. We herein report a chemical biology approach by using a rationally designed peptide inhibitor to disrupt the TLR4-MD2 association, thereby blocking TLR4 signaling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / antagonists & inhibitors*
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Cell Line
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Computational Biology
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Lymphocyte Antigen 96
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Mice
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Models, Molecular
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Peptides / chemical synthesis
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Peptides / pharmacology*
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Protein Binding / drug effects
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Protein Conformation
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Toll-Like Receptor 4 / antagonists & inhibitors*
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Toll-Like Receptor 4 / chemistry
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Toll-Like Receptor 4 / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Ly96 protein, mouse
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Lymphocyte Antigen 96
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Peptides
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Toll-Like Receptor 4