Key result
Identifying rare, function-disrupting mutations in platelet GPCRs provides important structure-function information with potential implications for pharmacotherapy and understanding bleeding disorders.
Studying rare platelet GPCR variants provides critical structure-function insights that may help optimize existing anti-platelet therapies and develop new treatments for arterial thrombosis.
Platelet-expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti-platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders.
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Nisar et al. (2014) conducted a review in Bleeding disorders and arterial thrombosis. Rare platelet GPCR variants was evaluated. Identifying rare, function-disrupting mutations in platelet GPCRs provides important structure-function information with potential implications for pharmacotherapy and understanding bleeding disorders.
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