P2X7 receptor: an emerging target in central nervous system diseases

被引:310
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
[121]   Electrophysiological classification of P2X7 receptors in rat cultured neocortical astroglia [J].
Noerenberg, W. ;
Schunk, J. ;
Fischer, W. ;
Sobottka, H. ;
Riedel, T. ;
Oliveira, J. F. ;
Franke, H. ;
Illes, P. .
BRITISH JOURNAL OF PHARMACOLOGY, 2010, 160 (08) :1941-1952
[122]   Clemastine Potentiates the Human P2X7 Receptor by Sensitizing It to Lower ATP Concentrations [J].
Noerenberg, Wolfgang ;
Hempel, Christoph ;
Urban, Nicole ;
Sobottka, Helga ;
Illes, Peter ;
Schaefer, Michael .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (13) :11067-11081
[123]   P2X Receptors as Drug Targets [J].
North, R. Alan ;
Jarvis, Michael F. .
MOLECULAR PHARMACOLOGY, 2013, 83 (04) :759-769
[124]   Rodent Cortical Astroglia Express In Situ Functional P2X7 Receptors Sensing Pathologically High ATP Concentrations [J].
Oliveira, Joao Filipe ;
Riedel, Thomas ;
Leichsenring, Anna ;
Heine, Claudia ;
Franke, Heike ;
Kruegel, Ute ;
Noerenberg, Wolfgang ;
Illes, Peter .
CEREBRAL CORTEX, 2011, 21 (04) :806-820
[125]   Gain-of-function of P2X7 receptor gene variants in multiple sclerosis [J].
Oyanguren-Desez, Olatz ;
Rodriguez-Antigueedad, Alfredo ;
Villoslada, Pablo ;
Domercq, Maria ;
Alberdi, Elena ;
Matute, Carlos .
CELL CALCIUM, 2011, 50 (05) :468-472
[126]   Connexin hemichannel and pannexin channel electrophysiology: How do they differ? [J].
Patel, Dakshesh ;
Zhang, Xian ;
Veenstra, Richard D. .
FEBS LETTERS, 2014, 588 (08) :1372-1378
[127]   Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury [J].
Peng, Weiguo ;
Cotrina, Maria L. ;
Han, Xiaoning ;
Yu, Hongmei ;
Bekar, Lane ;
Blum, Livnat ;
Takano, Takahiro ;
Tian, Guo-Feng ;
Goldman, Steven A. ;
Nedergaard, Maiken .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (30) :12489-12493
[128]   Synaptic localization of P2X7 receptors in the rat retina [J].
Puthussery, T ;
Fletcher, EL .
JOURNAL OF COMPARATIVE NEUROLOGY, 2004, 472 (01) :13-23
[129]   Single nucleotide polymorphisms that were identified in affective mood disorders affect ATP-activated P2X7 receptor functions [J].
Roger, Sebastien ;
Mei, Zhu-Zhong ;
Baldwin, Jocelyn M. ;
Dong, Li ;
Bradley, Helen ;
Baldwin, Stephen A. ;
Surprenant, Annmarie ;
Jiang, Lin-Hua .
JOURNAL OF PSYCHIATRIC RESEARCH, 2010, 44 (06) :347-355
[130]   Transcranial amelioration of inflammation and cell death after brain injury [J].
Roth, Theodore L. ;
Nayak, Debasis ;
Atanasijevic, Tatjana ;
Koretsky, Alan P. ;
Latour, Lawrence L. ;
McGavern, Dorian B. .
NATURE, 2014, 505 (7482) :223-+