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
[111]   Expression, assembly and function of novel C-terminal truncated variants of the mouse P2X7 receptor: re-evaluation of P2X7 knockouts [J].
Masin, Marianela ;
Young, Christopher ;
Lim, KoiNi ;
Barnes, Sara J. ;
Xu, Xing Jian ;
Marschall, Viola ;
Brutkowski, Wojciech ;
Mooney, Elizabeth R. ;
Gorecki, Dariusz C. ;
Murrell-Lagnado, Ruth .
BRITISH JOURNAL OF PHARMACOLOGY, 2012, 165 (04) :978-993
[112]   P2X7 receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis [J].
Matute, Carlos ;
Torre, Iratxe ;
Perez-Cerda, Fernando ;
Perez-Samartin, Alberto ;
Alberdi, Elena ;
Etxebarria, Estibaliz ;
Arranz, Amaia M. ;
Ravid, Rivka ;
Rodriguez-Antigueedad, Alfredo ;
Sanchez-Gomez, Maria Victoria ;
Domercq, Maria .
JOURNAL OF NEUROSCIENCE, 2007, 27 (35) :9525-9533
[113]   Case-control studies show that a non-conservative amino-acid change from a glutamine to arginine in the P2RX7 purinergic receptor protein is associated with both bipolar- and unipolar-affective disorders [J].
McQuillin, A. ;
Bass, N. J. ;
Choudhury, K. ;
Puri, V. ;
Kosmin, M. ;
Lawrence, J. ;
Curtis, D. ;
Gurling, H. M. D. .
MOLECULAR PSYCHIATRY, 2009, 14 (06) :614-620
[114]   P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone [J].
Messemer, Nanette ;
Kunert, Christin ;
Grohmann, Marcus ;
Sobottka, Helga ;
Nieber, Karen ;
Zimmermann, Herbert ;
Franke, Heike ;
Noerenberg, Wolfgang ;
Straub, Isabelle ;
Schaefer, Michael ;
Riedel, Thomas ;
Illes, Peter ;
Rubini, Patrizia .
NEUROPHARMACOLOGY, 2013, 73 :122-137
[115]   Up-regulation of P2X7 receptor-immunoreactivity by in vitro ischemia on the plasma membrane of cultured rat cortical neurons [J].
Milius, Doreen ;
Sperlagh, Beata ;
Illes, Peter .
NEUROSCIENCE LETTERS, 2008, 446 (01) :45-50
[116]   The P2X7 Receptor Drives Microglial Activation and Proliferation: A Trophic Role for P2X7R Pore [J].
Monif, Mastura ;
Reid, Christopher A. ;
Powell, Kim L. ;
Smart, Megan L. ;
Williams, David A. .
JOURNAL OF NEUROSCIENCE, 2009, 29 (12) :3781-3791
[117]   A Functional P2X7 Splice Variant with an Alternative Transmembrane Domain 1 Escapes Gene Inactivation in P2X7 Knock-out Mice [J].
Nicke, Annette ;
Kuan, Yung-Hui ;
Masin, Marianela ;
Rettinger, Juergen ;
Marquez-Klaka, Benjamin ;
Bender, Olaf ;
Gorecki, Dariusz C. ;
Murrell-Lagnado, Ruth D. ;
Soto, Florentina .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (38) :25813-25822
[118]   Mitochondrial dysfunction is involved in P2X7 receptor-mediated neuronal cell death [J].
Nishida, Kentaro ;
Nakatani, Tsunetoshi ;
Ohishi, Akihiro ;
Okuda, Hiroto ;
Higashi, Youichirou ;
Matsuo, Takaaki ;
Fujimoto, Sadaki ;
Nagasawa, Kazuki .
JOURNAL OF NEUROCHEMISTRY, 2012, 122 (06) :1118-1128
[119]   P2X7 Receptor Activation Mediates Retinal Ganglion Cell Death in a Human Retina Model of Ischemic Neurodegeneration [J].
Niyadurupola, Nuwan ;
Sidaway, Peter ;
Ma, Ning ;
Rhodes, Jeremy D. ;
Broadway, David C. ;
Sanderson, Julie .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2013, 54 (03) :2163-2170
[120]   Positive allosteric modulation by ivermectin of human but not murine P2X7 receptors [J].
Noerenberg, W. ;
Sobottka, H. ;
Hempel, C. ;
Ploetz, T. ;
Fischer, W. ;
Schmalzing, G. ;
Schaefer, M. .
BRITISH JOURNAL OF PHARMACOLOGY, 2012, 167 (01) :48-66