{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:21:56Z","timestamp":1791148916380,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,5]],"date-time":"2015-05-05T00:00:00Z","timestamp":1430784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurological manifestations in Lesch\u2010Nyhan disease (LND) are attributed to the effect of hypoxanthine\u2010guanine phosphoribosyltransferase (HPRT) deficiency on the nervous system development. HPRT deficiency causes the excretion of increased amounts of hypoxanthine into the extracellular medium and we hypothesized that HPRT deficiency related to hypoxanthine excess may then lead, directly or indirectly, to transcriptional aberrations in a variety of genes essential for the function and development of striatal progenitor cells. We have examined the effect of hypoxanthine excess on the differentiation of neurons in the well\u2010established human NTERA\u20102 cl.D1 (NT2\/D1) embryonic carcinoma neurogenesis model. NT2\/D1 cells differentiate along neuroectodermal lineages after exposure to retinoic acid (RA). Hypoxanthine effects on RA\u2010differentiation were examined by the changes on the expression of various transcription factor genes essential to neuronal differentiation and by the changes in tyrosine hydroxylase (TH), dopamine, adenosine and serotonin receptors (DRD, ADORA, HTR). We report that hypoxanthine excess deregulate WNT4, from Wnt\/\u03b2\u2010catenin pathway, and <jats:italic>engrailed<\/jats:italic> homeobox 1 gene and increased TH and dopamine DRD1, adenosine ADORA2A and serotonin HTR7 receptors, whose over expression characterize early neuro\u2010developmental processes.<\/jats:p>","DOI":"10.1007\/s10545-015-9854-4","type":"journal-article","created":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T09:47:49Z","timestamp":1430732869000},"page":"1109-1118","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Hypoxanthine deregulates genes involved in early neuronal development. Implications in Lesch\u2010Nyhan disease pathogenesis"],"prefix":"10.1002","volume":"38","author":[{"given":"R. J.","family":"Torres","sequence":"first","affiliation":[{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII Madrid Spain"},{"name":"Servicio de Bioqu\u00edmica, Edificio de Laboratorios, Planta 3 Hospital Universitario \u201cLa Paz\u201d Paseo de la Castellana 261 Madrid 28046 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. G.","family":"Puig","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Metabolic\u2010Vascular Unit La Paz University Hospital, IdiPaz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp164"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)02290-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02909-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90493-E"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199606133342403"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.11.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.07.006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9470-5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24191"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.178"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096575"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl056"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016572"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074967"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(64)90104-4"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1044"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0721139.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-05-01802.1992"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2007.01869.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200103000-00003"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)56968-X"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70238-2"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.155.3770.1682"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00149-4"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20031035"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5539"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19980701)53:1<78::AID-JNR8>3.0.CO;2-G"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-015-9854-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T04:42:21Z","timestamp":1694752941000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-015-9854-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,5]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1007\/s10545-015-9854-4"],"URL":"https:\/\/doi.org\/10.1007\/s10545-015-9854-4","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,5]]}}}