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Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics.

Abstract：

:The recognition of invading pathogens and endogenous molecules from damaged tissues by toll-like receptors (TLRs) triggers protective self-defense mechanisms. However, excessive TLR activation disrupts the immune homeostasis by sustained pro-inflammatory cytokines and chemokines production and consequently contributes to the development of many inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE), infection-associated sepsis, atherosclerosis, and asthma. Therefore, inhibitors/antagonists targeting TLR signals may be beneficial to treat these disorders. In this article, we first briefly summarize the pathophysiological role of TLRs in the inflammatory diseases. We then focus on reviewing the current knowledge in both preclinical and clinical studies of various TLR antagonists/inhibitors for the prevention and treatment of inflammatory diseases. These compounds range from conventional small molecules to therapeutic biologics and nanodevices. In particular, nanodevices are emerging as a new class of potent TLR inhibitors for their unique properties in desired bio-distribution, sustained circulation, and preferred pharmacodynamic and pharmacokinetic profiles. More interestingly, the inhibitory activity of these nanodevices can be regulated through precise nano-functionalization, making them the next generation therapeutics or "nano-drugs." Although, significant efforts have been made in developing different kinds of new TLR inhibitors/antagonists, only limited numbers of them have undergone clinical trials, and none have been approved for clinical uses to date. Nevertheless, these findings and continuous studies of TLR inhibition highlight the pharmacological regulation of TLR signaling, especially on multiple TLR pathways, as future promising therapeutic strategy for various inflammatory and autoimmune diseases.

journal_name

Front Physiol

journal_title

Frontiers in physiology

authors

Gao W,Xiong Y,Li Q,Yang H

doi

10.3389/fphys.2017.00508

subject

Has Abstract

pub_date

2017-07-19 00:00:00

pages

508

issn

1664-042X

journal_volume

pub_type

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Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics.