Mehta Nisha, Kaur Maninder, Singh Manjinder, Chand Sukhvir, Vyas Bhawna, Silakari Pragati, Bahia Malkeet Singh, Silakari Om
Molecular Modelling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
Department of Chemistry, Punjabi University, Patiala, 147002, Punjab, India.
Bioorg Med Chem. 2014 Jan 1;22(1):54-88. doi: 10.1016/j.bmc.2013.10.054. Epub 2013 Nov 11.
Purinergic receptors, also known as purinoceptors, are ligand gated membrane ion channels involved in many cellular functions. Among all identified purinergic receptors, P2X₇ subform is unique since it induces the caspase activity, cytokine secretion, and apoptosis. The distribution of P2X₇ receptors, and the need of high concentration of ATP required to activate this receptor exhibited its ability to function as 'danger' sensor associated with tissue inflammation and damage. Further, the modulation of other signalling pathways associated with P2X₇ has also been proposed to play an important role in the control of macrophage functions and inflammatory responses, especially towards lipopolysaccharides. Experimentally, researchers have also observed the decreased severity of inflammatory responses in P2X₇ receptor expressing gene (P2RX₇) knockout (KO) phenotypes. Therefore, newly developed potent antagonists of P2X₇ receptor would serve as novel therapeutic agents to combat various inflammatory conditions. In this review article, we tried to explore various aspects of P2X₇ receptors including therapeutic potential, and recent discoveries and developments of P2X₇ receptor antagonists.
嘌呤能受体,也被称为嘌呤受体,是参与多种细胞功能的配体门控膜离子通道。在所有已鉴定的嘌呤能受体中,P2X₇亚型是独特的,因为它能诱导半胱天冬酶活性、细胞因子分泌和细胞凋亡。P2X₇受体的分布以及激活该受体所需的高浓度三磷酸腺苷(ATP)表明其具有作为与组织炎症和损伤相关的“危险”传感器的功能。此外,与P2X₇相关的其他信号通路的调节也被认为在控制巨噬细胞功能和炎症反应中起重要作用,尤其是对脂多糖的反应。在实验中,研究人员还观察到在表达P2X₇受体基因(P2RX₇)敲除(KO)表型中炎症反应的严重程度降低。因此,新开发的强效P2X₇受体拮抗剂将作为对抗各种炎症病症的新型治疗药物。在这篇综述文章中,我们试图探讨P2X₇受体的各个方面,包括治疗潜力以及P2X₇受体拮抗剂的最新发现和进展。