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
[131]   Activation of Microglia by Amyloid β Requires P2X7 Receptor Expression [J].
Sanz, Juana M. ;
Chiozzi, Paola ;
Ferrari, Davide ;
Colaianna, Marilena ;
Idzko, Marco ;
Falzoni, Simonetta ;
Fellin, Renato ;
Trabace, Luigia ;
Di Virgilio, Francesco .
JOURNAL OF IMMUNOLOGY, 2009, 182 (07) :4378-4385
[132]   Alternative Splicing of the N-Terminal Cytosolic and Transmembrane Domains of P2X7 Controls Gating of the Ion Channel by ADP-Ribosylation [J].
Schwarz, Nicole ;
Drouot, Laurent ;
Nicke, Annette ;
Fliegert, Ralf ;
Boyer, Olivier ;
Guse, Andreas H. ;
Haag, Friedrich ;
Adriouch, Sahil ;
Koch-Nolte, Friedrich .
PLOS ONE, 2012, 7 (07)
[133]   P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis [J].
Sharp, Anthony J. ;
Polak, Paul E. ;
Simonini, Vittoria ;
Lin, Shao X. ;
Richardson, Jill C. ;
Bongarzone, Ernesto R. ;
Feinstein, Douglas L. .
JOURNAL OF NEUROINFLAMMATION, 2008, 5 (1)
[134]   Dynamic micro-organization of P2X7 receptors revealed by PALM based single particle tracking [J].
Shrivastava, Amulya N. ;
Rodriguez, Pamela C. ;
Triller, Antoine ;
Renner, Marianne .
FRONTIERS IN CELLULAR NEUROSCIENCE, 2013, 7
[135]  
Sikora A, 1999, J IMMUNOL, V163, P558
[136]   Reanalysis of P2X7 receptor expression in rodent brain [J].
Sim, JA ;
Young, MT ;
Sung, HY ;
North, RA ;
Surprenant, A .
JOURNAL OF NEUROSCIENCE, 2004, 24 (28) :6307-6314
[137]   Altered cytokine production in mice lacking P2X7 receptors [J].
Solle, M ;
Labasi, J ;
Perregaux, DG ;
Stam, E ;
Petrushova, N ;
Koller, BH ;
Griffiths, RJ ;
Gabel, CA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (01) :125-132
[138]   Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity [J].
Sorge, Robert E. ;
Trang, Tuan ;
Dorfman, Ruslan ;
Smith, Shad B. ;
Beggs, Simon ;
Ritchie, Jennifer ;
Austin, Jean-Sebastien ;
Zaykin, Dmitri V. ;
Vander Meulen, Heather ;
Costigan, Michael ;
Herbert, Teri A. ;
Yarkoni-Abitbul, Merav ;
Tichauer, David ;
Livneh, Jessica ;
Gershon, Edith ;
Zheng, Ming ;
Tan, Keith ;
John, Sally L. ;
Slade, Gary D. ;
Jordan, Joanne ;
Woolf, Clifford J. ;
Peltz, Gary ;
Maixner, William ;
Diatchenko, Luda ;
Seltzer, Ze'ev ;
Salter, Michael W. ;
Mogil, Jeffrey S. .
NATURE MEDICINE, 2012, 18 (04) :595-599
[139]   P2RX7 Gene Is Associated Consistently with Mood Disorders and Predicts Clinical Outcome in Three Clinical Cohorts [J].
Soronen, Pia ;
Mantere, Outi ;
Melartin, Tarja ;
Suominen, Kirsi ;
Vuorilehto, Maria ;
Rytsala, Heikki ;
Arvilommi, Petri ;
Holma, Irina ;
Holma, Mikael ;
Jylha, Pekka ;
Valtonen, Hanna M. ;
Haukka, Jari ;
Isometsa, Erkki ;
Paunio, Tiina .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2011, 156B (04) :435-447
[140]   Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus [J].
Sperlágh, B ;
Köfalvi, A ;
Deuchars, J ;
Atkinson, L ;
Milligan, CJ ;
Buckley, NJ ;
Vizi, ES .
JOURNAL OF NEUROCHEMISTRY, 2002, 81 (06) :1196-1211