P2X7 receptor: an emerging target in central nervous system diseases

被引:325
作者
Sperlagh, Beata [1 ]
Illes, Peter [2 ]
机构
[1] Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1450 Budapest, Hungary
[2] Univ Leipzig, Rudolf Boehm Inst Pharmacol & Toxicol, D-04107 Leipzig, Germany
基金
欧洲研究理事会;
关键词
P2X7; receptor; ATP; neurodegenerative diseases; psychiatric disorders; PREVENTS ATP EXCITOTOXICITY; P2X(7) PURINERGIC RECEPTOR; GLUTAMATE RELEASE; STATUS EPILEPTICUS; ION-CHANNEL; RHEUMATOID-ARTHRITIS; PLASMA-MEMBRANE; GENE-EXPRESSION; KNOCKOUT MICE; DORSAL-HORN;
D O I
10.1016/j.tips.2014.08.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The ATP-sensitive homomeric P2X7 receptor (P2X7R) has received particular attention as a potential drug target because of its widespread involvement in inflammatory diseases as a key regulatory element of the inflammasome complex. However, it has only recently become evident that P2X7Rs also play a pivotal role in central nervous system (CNS) pathology. There is an explosion of data indicating that genetic deletion and pharmacological blockade of P2X7Rs alter responsiveness in animal models of neurological disorders, such as stroke, neurotrauma, epilepsy, neuropathic pain, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and Huntington's disease. Moreover, recent studies suggest that P2X7Rs regulate the pathophysiology of psychiatric disorders, including mood disorders, implicating P2X7Rs as drug targets in a variety of CNS pathology.
引用
收藏
页码:537 / 547
页数:11
相关论文
共 161 条
[1]   Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X7 receptor [J].
Abberley, Lee ;
Bebius, Aude ;
Beswick, Paul J. ;
Billinton, Andy ;
Collis, Katharine L. ;
Dean, David K. ;
Fonfria, Elena ;
Gleave, Robert J. ;
Medhurst, Stephen J. ;
Michel, Anton D. ;
Moses, Andrew P. ;
Patel, Sadhana ;
Roman, Shilina A. ;
Scoccitti, Tiziana ;
Smith, Beverley ;
Steadman, Jon G. A. ;
Walter, Daryl S. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (22) :6370-6374
[2]   Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat [J].
Able, S. L. ;
Fish, R. L. ;
Bye, H. ;
Booth, L. ;
Logan, Y. R. ;
Nathaniel, C. ;
Hayter, P. ;
Katugampola, S. D. .
BRITISH JOURNAL OF PHARMACOLOGY, 2011, 162 (02) :405-414
[3]   Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor [J].
Adinolfi, Elena ;
Cirillo, Maria ;
Woltersdorf, Ronja ;
Falzoni, Simonetta ;
Chiozzi, Paola ;
Pellegatti, Patrizia ;
Callegari, Maria Giulia ;
Sandona, Doriana ;
Markwardt, Fritz ;
Schmalzing, Guenther ;
Di Virgilio, Francesco .
FASEB JOURNAL, 2010, 24 (09) :3393-3404
[4]   ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site [J].
Adriouch, Sahil ;
Bannas, Peter ;
Schwarz, Nicole ;
Fliegert, Ralf ;
Guse, Andreas H. ;
Seman, Michel ;
Haag, Friedrich ;
Koch-Nolte, Friedrich .
FASEB JOURNAL, 2008, 22 (03) :861-869
[5]   Is pannexin the pore associated with the P2X7 receptor? [J].
Alberto, A. V. P. ;
Faria, R. X. ;
Couto, C. G. C. ;
Ferreira, L. G. B. ;
Souza, C. A. M. ;
Teixeira, P. C. N. ;
Froes, M. M. ;
Alves, L. A. .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2013, 386 (09) :775-787
[6]   Pharmacokinetic and pharmacodynamic profiling of a P2X7 receptor allosteric modulator GSK1482160 in healthy human subjects [J].
Ali, Zahid ;
Laurijssens, Bart ;
Ostenfeld, Thor ;
McHugh, Simon ;
Stylianou, Anastasia ;
Scott-Stevens, Paul ;
Hosking, Louise ;
Dewit, Odile ;
Richardson, Jill C. ;
Chen, Chao .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 75 (01) :197-207
[7]   Evidence for two conductive pathways in P2X7 receptor: differences in modulation and selectivity [J].
Alloisio, Susanna ;
Di Garbo, Angelo ;
Barbieri, Raffaella ;
Bozzo, Luigi ;
Ferroni, Stefano ;
Nobile, Mario .
JOURNAL OF NEUROCHEMISTRY, 2010, 113 (03) :796-806
[8]   Purinergic signalling at the plasma membrane: a multipurpose and multidirectional mode to deal with amyotrophic lateral sclerosis and multiple sclerosis [J].
Amadio, Susanna ;
Apolloni, Savina ;
D'Ambrosi, Nadia ;
Volonte, Cinzia .
JOURNAL OF NEUROCHEMISTRY, 2011, 116 (05) :796-805
[9]   A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain [J].
Ando, R. D. ;
Mehesz, B. ;
Gyires, K. ;
Illes, P. ;
Sperlagh, B. .
BRITISH JOURNAL OF PHARMACOLOGY, 2010, 159 (05) :1106-1117
[10]   P2X4 receptors interact with both P2X2 and P2X7 receptors in the form of homotrimers [J].
Antonio, L. S. ;
Stewart, A. P. ;
Xu, X. J. ;
Varanda, W. A. ;
Murrell-Lagnado, R. D. ;
Edwardson, J. M. .
BRITISH JOURNAL OF PHARMACOLOGY, 2011, 163 (05) :1069-1077