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• W2035711257 endingPage "38" @default.
• W2035711257 startingPage "29" @default.
• W2035711257 abstract "The Toll-like receptor (TLR) family plays a fundamental role in host innate immunity by mounting a rapid and potent inflammatory response to pathogen infection. TLRs recognize distinct microbial components and activate intracellular signaling pathways that induce expression of host inflammatory genes. Extensive research in the past decade to understand TLR-mediated mechanisms of innate immunity has enabled pharmaceutical companies to begin to develop novel therapeutics for the purpose of controlling inflammatory disease. Initially, extracellular TLR agonists were designed to compete with natural microbial ligands for binding to TLRs. More recently, basic research to identify new targets for drug development has begun to explore modulation of TLR intracellular signaling pathways, in addition to TLR ligand binding. In this review, we will discuss recent strategies, including the use of decoy peptides and mimetics, plant polyphenols, and chemically modified antisense oligonucleotides, that inhibit different molecular events in TLR signaling pathways to modulate the inflammatory response. The molecular mechanisms of these inhibitors range from interference with protein-protein interactions between signaling proteins, to inhibition of transcription factor activity, to perturbation of the plasma membrane, and are derived from host, pathogen, and plant sources and by rational design. Taken together, these studies represent promising avenues for the development of novel tailored immune therapeutics that can relieve the great toll inflicted by inflammatory disease on human health and quality of life. Keywords: Toll-like receptors, anti-inflammatory agents, innate immunity, drug design, inhibitory peptides, plant polyphenols, BB loop, TIR domain" @default.
• W2035711257 created "2016-06-24" @default.
• W2035711257 creator A5023810299 @default.
• W2035711257 creator A5048326191 @default.
• W2035711257 creator A5057163156 @default.
• W2035711257 date "2008-03-01" @default.
• W2035711257 modified "2023-10-16" @default.
• W2035711257 title "Targeting Toll-Like Receptor Signaling Pathways for Design of Novel Immune Therapeutics" @default.
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