Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.
Journal
Thrombosis journal
ISSN: 1477-9560
Titre abrégé: Thromb J
Pays: England
ID NLM: 101170542
Informations de publication
Date de publication:
2019
2019
Historique:
received:
20
11
2018
accepted:
08
03
2019
entrez:
13
4
2019
pubmed:
13
4
2019
medline:
13
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30976204
doi: 10.1186/s12959-019-0194-8
pii: 194
pmc: PMC6440139
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
4Commentaires et corrections
Type : ErratumIn
Déclaration de conflit d'intérêts
Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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