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
  • [61] Genetics of the P2X7 receptor and human disease
    Fuller, Stephen J.
    Stokes, Leanne
    Skarratt, Kristen K.
    Gu, Ben J.
    Wiley, James S.
    [J]. PURINERGIC SIGNALLING, 2009, 5 (02) : 257 - 262
  • [62] P2X7 receptor-induced death of motor neurons by a peroxynitrite/FAS-dependent pathway
    Gandelman, Mandi
    Levy, Mark
    Cassina, Patricia
    Barbeito, Luis
    Beckman, Joseph S.
    [J]. JOURNAL OF NEUROCHEMISTRY, 2013, 126 (03) : 382 - 388
  • [63] Extracellular ATP and the P2X7 receptor in astrocyte-mediated motor neuron death: implications for amyotrophic lateral sclerosis
    Gandelman, Mandi
    Peluffo, Hugo
    Beckman, Joseph S.
    Cassina, Patricia
    Barbeito, Luis
    [J]. JOURNAL OF NEUROINFLAMMATION, 2010, 7
  • [64] The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System
    Garcia-Huerta, Paula
    Diaz-Hernandez, Miguel
    Delicado, Esmerilda G.
    Pimentel-Santillana, Maria
    Teresa Miras-Portugal, Ma
    Gomez-Villafuertes, Rosa
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (53) : 44628 - 44644
  • [65] Differential effects of undernourishment on the differentiation and maturation of rat enteric neurons
    Girotti, Priscila Azevedo
    Misawa, Rubia
    Palombit, Kelly
    Mendes, Cristina Eusebio
    Bittencourt, Jackson Cioni
    Castelucci, Patricia
    [J]. CELL AND TISSUE RESEARCH, 2013, 353 (03) : 367 - 380
  • [66] Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X7 antagonists
    Gleave, Robert J.
    Walter, Daryl S.
    Beswick, Paul J.
    Fonfria, Elena
    Michel, Anton D.
    Roman, Shilina A.
    Tang, Sac-Pham
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (16) : 4951 - 4954
  • [67] Effect of genetic deletion and pharmacological antagonism of P2X7 receptors in a mouse animal model of migraine
    Goeloencser, Flora
    Sperlagh, Beata
    [J]. JOURNAL OF HEADACHE AND PAIN, 2014, 15 : 1 - 8
  • [68] Variation in P2RX7 Candidate Gene (rs2230912) Is Not Associated With Bipolar I Disorder and Unipolar Major Depression in Four European Samples
    Grigoroiu-Serbanescu, Maria
    Herms, Stefan
    Muehleisen, Thomas W.
    Georgi, Alexander
    Diaconu, Carmen C.
    Strohmaier, Jana
    Czerski, Piotr
    Hauser, Joanna
    Leszczynska-Rodziewicz, Anna
    Jamra, Rami Abou
    Babadjanova, Gulia
    Tiganov, A.
    Krasnov, V.
    Kapiletti, Sofia
    Neagu, Ana Lulia
    Vollmer, Jennifer
    Breuer, Rene
    Rietschel, Marcella
    Propping, Peter
    Noethen, Markus M.
    Cichon, Sven
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2009, 150B (07) : 1017 - 1021
  • [69] Temporal expression of P2X7 purinergic receptor during the course of experimental autoimmune encephalomyelitis
    Grygorowicz, Tomasz
    Struzynska, Lidia
    Sulkowski, Grzegorz
    Chalimoniuk, Malgorzata
    Sulejczak, Dorota
    [J]. NEUROCHEMISTRY INTERNATIONAL, 2010, 57 (07) : 823 - 829
  • [70] P2X7 Is a Scavenger Receptor for Apoptotic Cells in the Absence of Its Ligand, Extracellular ATP
    Gu, Ben J.
    Saunders, Bernadette M.
    Petrou, Steven
    Wiley, James S.
    [J]. JOURNAL OF IMMUNOLOGY, 2011, 187 (05) : 2365 - 2375