Abstract
The identification of the TLRs as key sensors of microbial infection has presented a series of new targets for drug development. The TLRs are linked to the most powerful inflammatory pathways in mammals. The question arises from the start: do we wish to stimulate TLR signaling in order to eradicate specific infections and/or neoplastic diseases? Or do we wish to block TLR signaling to treat inflammatory diseases? If we accept that it would be useful to modulate TLR signaling, the next step is to identify the correct molecular target(s) for the task. Perhaps it might even be possible to exercise selectivity, modulating some aspects of TLR signaling and not others. Classical and reverse genetic analyses offer insight into the possibilities that exist, and point to specific checkpoints within signaling pathways at which modulation might normally be imposed.
Keywords: TNF neutralization, sterile inflammation, microbial adjuvants, MyD88-dependent signal transduction, Trif mutation
Current Pharmaceutical Design
Title: TLR Signaling Pathways: Opportunities for Activation and Blockade in Pursuit of Therapy
Volume: 12 Issue: 32
Author(s): K. Hoebe, Z. Jiang, P. Georgel, K. Tabeta, E. Janssen, X. Du and B. Beutler
Affiliation:
Keywords: TNF neutralization, sterile inflammation, microbial adjuvants, MyD88-dependent signal transduction, Trif mutation
Abstract: The identification of the TLRs as key sensors of microbial infection has presented a series of new targets for drug development. The TLRs are linked to the most powerful inflammatory pathways in mammals. The question arises from the start: do we wish to stimulate TLR signaling in order to eradicate specific infections and/or neoplastic diseases? Or do we wish to block TLR signaling to treat inflammatory diseases? If we accept that it would be useful to modulate TLR signaling, the next step is to identify the correct molecular target(s) for the task. Perhaps it might even be possible to exercise selectivity, modulating some aspects of TLR signaling and not others. Classical and reverse genetic analyses offer insight into the possibilities that exist, and point to specific checkpoints within signaling pathways at which modulation might normally be imposed.
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Cite this article as:
Hoebe K., Jiang Z., Georgel P., Tabeta K., Janssen E., Du X. and Beutler B., TLR Signaling Pathways: Opportunities for Activation and Blockade in Pursuit of Therapy, Current Pharmaceutical Design 2006; 12 (32) . https://dx.doi.org/10.2174/138161206778743466
DOI https://dx.doi.org/10.2174/138161206778743466 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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