![]() ![]() Another mechanism might be that of cancer cells expressing a structurally altered P2RX7 receptor, devoid of the LP function. Furthermore, how can tumor cells take advantage of P2RX7 for growth and spread and yet survive overexpression of potentially cytotoxic LP in the eATP-rich environment? The recent discovery of the feedback loop, wherein the LP-evoked release of active MMP-2 triggers the receptor cleavage, provided one explanation. Not only the molecular mechanism of LP opening is still not fully understood but its function(s) are also unclear. Firstly, this receptor functions as an ion channel, but its chronic stimulation by high eATP causes opening of the non-selective large pore (LP), which can trigger cell death. ![]() However, several unanswered questions limit the cogent development of P2RX7 therapies. The availability of crystal structures allows rational design of improved antagonists and modeling of binding sites of the known or presumed inhibitors. Interestingly, the recent crystallization of mammalian and chicken receptors revealed that most widely-used antagonists may bind a unique allosteric site. As a result, a range of P2RX7 antagonists have been developed and trialed. Subsequently, P2RX7 signaling has been documented in other physiological and pathological processes including pain, CNS and psychiatric disorders and cancer. Therefore, P2RX7 has been long investigated as a target in the treatment of infectious and inflammatory diseases. The P2RX7 receptor is a unique member of a family of extracellular ATP (eATP)-gated ion channels expressed in immune cells, where its activation triggers the inflammatory cascade. 3The General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, Warsaw, Poland.2Faculty of Health and Life Sciences, The School of Allied Health Sciences, De Montfort University, Leicester, United Kingdom.1Molecular Medicine Laboratory, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom.(a) The FSF's Back-Cover Text is: “You have the freedom to copy and A copy of the license is included in the section entitled Version 1.3 or any later version published by the Free Softwareįoundation with no Invariant Sections, with the Front-Cover textsīeing “A GNU Manual,” and with the Back-Cover Texts as in Under the terms of the GNU Free Documentation License, Permission is granted to copy, distribute and/or modify this document Appendix A GNU Free Documentation License.20.7 Header Present But Cannot Be Compiled.20.5 How Do I #define Installation Directories?.20 Frequent Autoconf Questions, with answers. ![]()
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