{"title":"P2Y6R与CYSLTR2在动脉粥样硬化中作为长链神经酰胺的内源性受体。","authors":"Qing Ye, Yong Tang","doi":"10.1007/s11302-025-10090-x","DOIUrl":null,"url":null,"abstract":"<p><p>In a recent article published in Nature, 2025 Zhang et al. identified the pyrimidinergic receptor P2Y<sub>6</sub> (P2Y<sub>6</sub>R), together with the cysteinyl leukotriene receptor 2 (CYSLTR2), as key receptor mediating ceramide-induced atherosclerotic cardiovascular disease (ASCVD). High levels of plasma ceramides bind to P2Y<sub>6</sub>R and CYSLTR2, activating the Gαq signaling pathway, which triggers NLRP3 inflammasome activation and the release of the pro-inflammatory cytokine IL-1β, thereby accelerating the progression of atherosclerosis. These findings provide credible evidence supporting the long-chain ceramides as clinical predictors for risks of ASCVD. Designing small-molecule drugs and antagonists that target the binding sites of ceramide-CYSLTR2/P2Y<sub>6</sub>R complexes presents a potential clinical strategy beyond traditional lipid-lowering therapies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"P2Y<sub>6</sub>R together with CYSLTR2 serves as endogenous receptor for long-chain ceramides in atherosclerosis.\",\"authors\":\"Qing Ye, Yong Tang\",\"doi\":\"10.1007/s11302-025-10090-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In a recent article published in Nature, 2025 Zhang et al. identified the pyrimidinergic receptor P2Y<sub>6</sub> (P2Y<sub>6</sub>R), together with the cysteinyl leukotriene receptor 2 (CYSLTR2), as key receptor mediating ceramide-induced atherosclerotic cardiovascular disease (ASCVD). High levels of plasma ceramides bind to P2Y<sub>6</sub>R and CYSLTR2, activating the Gαq signaling pathway, which triggers NLRP3 inflammasome activation and the release of the pro-inflammatory cytokine IL-1β, thereby accelerating the progression of atherosclerosis. These findings provide credible evidence supporting the long-chain ceramides as clinical predictors for risks of ASCVD. Designing small-molecule drugs and antagonists that target the binding sites of ceramide-CYSLTR2/P2Y<sub>6</sub>R complexes presents a potential clinical strategy beyond traditional lipid-lowering therapies.</p>\",\"PeriodicalId\":20952,\"journal\":{\"name\":\"Purinergic Signalling\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-05-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Purinergic Signalling\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11302-025-10090-x\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Purinergic Signalling","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11302-025-10090-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
P2Y6R together with CYSLTR2 serves as endogenous receptor for long-chain ceramides in atherosclerosis.
In a recent article published in Nature, 2025 Zhang et al. identified the pyrimidinergic receptor P2Y6 (P2Y6R), together with the cysteinyl leukotriene receptor 2 (CYSLTR2), as key receptor mediating ceramide-induced atherosclerotic cardiovascular disease (ASCVD). High levels of plasma ceramides bind to P2Y6R and CYSLTR2, activating the Gαq signaling pathway, which triggers NLRP3 inflammasome activation and the release of the pro-inflammatory cytokine IL-1β, thereby accelerating the progression of atherosclerosis. These findings provide credible evidence supporting the long-chain ceramides as clinical predictors for risks of ASCVD. Designing small-molecule drugs and antagonists that target the binding sites of ceramide-CYSLTR2/P2Y6R complexes presents a potential clinical strategy beyond traditional lipid-lowering therapies.
期刊介绍：
Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
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