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However synaptic alterations and increased susceptibility to neuronal death are known contributors to Huntington's disease (HD) symptomatology. While decreased metabolism has long been associated with HD,  recent findings have surprisingly demonstrated reduced neuronal apoptosis in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    and\n                    <jats:italic>Drosophila<\/jats:italic>\n                    models of HD by drugs that diminish ATP production. Interestingly, extracellular ATP has been recently reported to elicit neuronal death through stimulation of P2X7 receptors. These are ATP\u2010gated cation channels known to modulate neurotransmitter release from neuronal presynaptic terminals and to regulate cytokine production and release from microglia. We hypothesized that alteration in P2X7\u2010mediated calcium permeability may contribute to HD synaptic dysfunction and increased neuronal apoptosis. Using mouse and cellular models of HD,  we demonstrate increased P2X7\u2010receptor level and altered P2X7\u2010mediated calcium permeability in somata and terminals of HD neurons. Furthermore,  cultured neurons expressing mutant huntingtin showed increased susceptibility to apoptosis triggered by P2X7\u2010receptor stimulation. Finally,\n                    <jats:italic>in vivo<\/jats:italic>\n                    administration of the P2X7\u2010antagonist Brilliant Blue\u2010G (BBG) to HD mice prevented neuronal apoptosis and attenuated body weight loss and motor\u2010coordination deficits. These\n                    <jats:italic>in vivo<\/jats:italic>\n                    data strongly suggest that altered P2X7\u2010receptor level and function contribute to HD pathogenesis and highlight the therapeutic potential of P2X7 receptor antagonists.\u2014Diaz\u2010Hernandez, M., Diez\u2010Zaera, M., Sanchez\u2010Nogueiro, J., Gomez\u2010Villafuertes, R., Canals, J.M., Alberch, J., Miras\u2010Portugal, M.T., Lucas, J.J. Altered P2X7\u2010receptor level and function in mouse models of Huntington's disease and therapeutic efficacy of antagonist administration.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 1893\u20131906 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-122275","type":"journal-article","created":{"date-parts":[[2009,1,26]],"date-time":"2009-01-26T20:44:18Z","timestamp":1233002658000},"page":"1893-1906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":190,"title":["Altered P2X7\u2010receptor level and function in mouse models of Huntington's disease and therapeutic efficacy of antagonist administration"],"prefix":"10.1096","volume":"23","author":[{"given":"Miguel","family":"D\u00edaz-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular \u201cSevero Ochoa\u201d Consejo Superior de Investigaci\u00f2nes Cientificas Universidad Auton\u00f3ma de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas Instituto de Salud Carlos III Madrid Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular IV Facultad de Veterinaria Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"D\u00edez-Zaera","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"S\u00e1nchez-Nogueiro","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular \u201cSevero Ochoa\u201d Consejo Superior de Investigaci\u00f2nes Cientificas Universidad Auton\u00f3ma de Madrid Madrid Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular IV Facultad de Veterinaria Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"G\u00f3mez-Villafuertes","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular IV Facultad de Veterinaria Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Canals","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas Instituto de Salud Carlos III Madrid Spain"},{"name":"Departament de Biologia Cellular i Anatomia Patol\u00f4gica Facultat de Medicina Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Alberch","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas Instituto de Salud Carlos III Madrid Spain"},{"name":"Departament de Biologia Cellular i Anatomia Patol\u00f4gica Facultat de Medicina Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Miras-Portugal","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular IV Facultad de Veterinaria Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 J.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular \u201cSevero Ochoa\u201d Consejo Superior de Investigaci\u00f2nes Cientificas Universidad Auton\u00f3ma de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00872-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7222-8"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400250"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2003.08.006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nrn1100","article-title":"Targeting programmed cell death in neurodegenerative diseases","volume":"4","author":"Vila M.","year":"2003","journal-title":"Nat. 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