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Cited by 371

The DOI matches its Crossref record; 296 of the 296 references it cites were found in a registry or an index.

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

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Heuberger, Dorothea M., Schuepbach, Reto A.·2019·Thrombosis Journal
DOI 10.1186/s12959-019-0194-8
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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

Authors
Heuberger, D. M., & Schuepbach, R. A.
Venue
Thrombosis Journal
Publisher
Springer Science and Business Media LLC
Published
2019-03-29
Volume
17
Issue
1
Pages
22-22
ISSN
1477-9560 (ISSN-L)
DOI
10.1186/s12959-019-0194-8
OpenAlex
W2938493336
Cited by
371
References
296
FWCI
24.17
Type
journal article
Language
en
Update notices
correction (2019-11-06)
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (tdm)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (#PZ00P3_136639)

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Heuberger, D. M., & Schuepbach, R. A. (2019). Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases. Thrombosis Journal. https://doi.org/10.1186/s12959-019-0194-8

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