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Thrombosis Journal
Published in: Thrombosis Journal 1/2019

Open Access 01-12-2019 | Review

Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases

Authors: Dorothea M. Heuberger, Reto A. Schuepbach

Published in: Thrombosis Journal | Issue 1/2019

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Abstract

Inflammatory diseases have become increasingly prevalent with industrialization. To address this, numerous anti-inflammatory agents and molecular targets have been considered in clinical trials. Among molecular targets, protease-activated receptors (PARs) are abundantly recognized for their roles in the development of chronic inflammatory diseases. In particular, several inflammatory effects are directly mediated by the sensing of proteolytic activity by PARs.
PARs belong to the seven transmembrane domain G protein-coupled receptor family, but are unique in their lack of physiologically soluble ligands. In contrast with classical receptors, PARs are activated by N-terminal proteolytic cleavage. Upon removal of specific N-terminal peptides, the resulting N-termini serve as tethered activation ligands that interact with the extracellular loop 2 domain and initiate receptor signaling. In the classical pathway, activated receptors mediate signaling by recruiting G proteins. However, activation of PARs alternatively lead to the transactivation of and signaling through receptors such as co-localized PARs, ion channels, and toll-like receptors.
In this review we consider PARs and their modulators as potential therapeutic agents, and summarize the current understanding of PAR functions from clinical and in vitro studies of PAR-related inflammation.
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Metadata
Title
Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases
Authors
Dorothea M. Heuberger
Reto A. Schuepbach
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2019
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-019-0194-8

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