Protease-activated Receptor 4: from Structure to Function and Back Again

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2016 Feb 5

PMID 26844674

Citations 23

Authors

Shauna L French

Justin R Hamilton

Affiliations

Soon will be listed here.

Abstract

Protease-activated receptors are a family of four GPCRs (PAR1-PAR4) with a number of unique attributes. Nearly two and a half decades after the discovery of the first PAR, an antagonist targeting this receptor has been approved for human use. The first-in-class PAR1 antagonist, vorapaxar, was approved for use in the USA in 2014 for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. These recent developments indicate the clinical potential of manipulating PAR function. While much work has been aimed at uncovering the function of PAR1 and, to a lesser extent, PAR2, comparatively little is known regarding the pharmacology and physiology of PAR3 and PAR4. Recent studies have begun to develop the pharmacological and genetic tools required to study PAR4 function in detail, and there is now emerging evidence for the function of PAR4 in disease settings. In this review, we detail the discovery, structure, pharmacology, physiological significance and therapeutic potential of PAR4. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

Citing Articles

Elevated protease-activated receptor 4 (PAR4) gene expression in Alzheimer's disease predicts cognitive decline.

Winfree R, Erreger K, Phillips J, Seto M, Wang Y, Schneider J Neurobiol Aging. 2024; 140:93-101.

PMID: 38761538 PMC: 11610797. DOI: 10.1016/j.neurobiolaging.2024.04.007.

The thrombin receptor PAR4 supports visceral adipose tissue inflammation.

Kleeschulte S, Fischinger V, Ohlke L, Bode J, Kamler M, Dobrev D Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(9):7187-7200.

PMID: 38652276 PMC: 11422268. DOI: 10.1007/s00210-024-03097-5.

Unraveling the Molecular Mechanisms of Activated Protein C (APC) in Mitigating Reperfusion Injury and Cardiac Ischemia: a Promising Avenue for Novel Therapeutic Interventions.

Johri N, Matreja P, Agarwal S, Nagar P, Kumar D, Maurya A J Cardiovasc Transl Res. 2023; 17(2):345-355.

PMID: 37851312 DOI: 10.1007/s12265-023-10445-y.

Species Differences in Platelet Protease-Activated Receptors.

Renna S, McKenzie S, Michael J Int J Mol Sci. 2023; 24(9).

PMID: 37176005 PMC: 10179473. DOI: 10.3390/ijms24098298.

PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells.

Heo Y, Jeon H, Namkung W Int J Mol Sci. 2022; 23(2).

PMID: 35054966 PMC: 8775998. DOI: 10.3390/ijms23020776.

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