{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:41:56Z","timestamp":1791114116410,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,7,29]],"date-time":"2009-07-29T00:00:00Z","timestamp":1248825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001671","name":"Hereditary Disease Foundation","doi-asserted-by":"crossref","award":["2008A051302"],"award-info":[{"award-number":["2008A051302"]}],"id":[{"id":"10.13039\/100001671","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["NS35711"],"award-info":[{"award-number":["NS35711"]}]},{"name":"NIH","award":["NS038194"],"award-info":[{"award-number":["NS038194"]}]},{"name":"HighQ Foundation\/CHDI"},{"DOI":"10.13039\/100000887","name":"Huntington's Disease Society of America","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000887","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fundacion Mexico en Harvard A.C."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with Huntington's disease have an expanded polyglutamine tract in huntingtin and suffer severe brain atrophy and neurodegeneration. Because membrane dysfunction can occur in Huntington's disease, we addressed whether mutant huntingtin in brain and primary neurons is present in lipid rafts, which are cholesterol\u2010enriched membrane domains that mediate growth and survival signals. Biochemical analysis of detergent\u2010resistant membranes from brains and primary neurons of wild\u2010type and presymptomatic Huntington's disease knock\u2010in mice showed that wild\u2010type and mutant huntingtin were recovered in lipid raft\u2010enriched detergent\u2010resistant membranes. The association with lipid rafts was stronger for mutant huntingtin than wild\u2010type huntingtin. Lipid rafts extracted from Huntington's disease mice had normal levels of lipid raft markers (G<jats:sub>\u03b1q<\/jats:sub>, Ras, and flotillin) but significantly more glycogen synthase kinase 3\u2010\u03b2. Increases in glycogen synthase kinase 3\u2010\u03b2 have been associated with apoptotic cell death. Treating Huntington's disease primary neurons with inhibitors of glycogen synthase kinase 3\u2010\u03b2 reduced neuronal death. We speculate that accumulation of mutant huntingtin and glycogen synthase kinase 3\u2010\u03b2 in lipid rafts of presymptomatic Huntington's disease mouse neurons contributes to neurodegeneration in Huntington's disease. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22184","type":"journal-article","created":{"date-parts":[[2009,7,29]],"date-time":"2009-07-29T17:04:13Z","timestamp":1248887053000},"page":"179-190","source":"Crossref","is-referenced-by-count":86,"title":["Mutant huntingtin and glycogen synthase kinase 3\u2010\u03b2 accumulate in neuronal lipid rafts of a presymptomatic knock\u2010in mouse model of Huntington's disease"],"prefix":"10.1002","volume":"88","author":[{"given":"Antonio","family":"Valencia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick B.","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Sapp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly B.","family":"Kegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Chase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Aronin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"DiFiglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2006.12.003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1999.0451"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411642200"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.8.4971"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00287-4"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1971.tb00289.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204861200"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh162"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-07-0726"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05523.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90346-1"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200201098"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01423"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3590001"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/29570"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709555200"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309348200"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90352-G"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12419.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(01)00011-9"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.64.2.172"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.08.041"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00973-9"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211785200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.02.010"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033435"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5253"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503672200"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.5.1645"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04191.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.12.188"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700168"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.10.055"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e328315cd4c"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704704200"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03473"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.2.137"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.05948.x"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10776"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603845200"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.10.013"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02849.x"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200710061"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0106-08.2008"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(07)38017-8"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.029"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2005.05.005"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800040-JLR200"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.35.22298"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503805200"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.498923"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.148.5.997"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000169025.09670.6d"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/147323000803600505"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0908525"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.08.013"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036052"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.17.1953"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110338200"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.05.087"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03620.x"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.11.037"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01572.x"},{"key":"e_1_2_6_66_1","first-page":"1582","article-title":"Randomized controlled trial of ethyl\u2010eicosapentaenoic acid in Huntington disease: the TREND\u2010HD study","volume":"65","author":"TREND\u2010HD Study","year":"2008","journal-title":"Arch Neurol"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.09.006"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3355-05.2005"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/29563"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600066"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2008.05.015"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1702"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.22184","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.22184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T08:15:03Z","timestamp":1698912903000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.22184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,29]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,1]]}},"alternative-id":["10.1002\/jnr.22184"],"URL":"https:\/\/doi.org\/10.1002\/jnr.22184","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,29]]}}}