{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:10:24Z","timestamp":1764493824294,"version":"3.37.3"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,6,13]],"date-time":"2015-06-13T00:00:00Z","timestamp":1434153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Danish Huntington's Disease Association Research Foundation"},{"DOI":"10.13039\/501100003035","name":"Aase and Ejnar Danielsen Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003035","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Director Jacob Madsen and Wife Olga Madsen's Foundation"},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001734","name":"University of Copenhagen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001734","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease\u2010modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene\u2010expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene\u2010expansion negative individuals using surface\u2010enhanced laser desorption\/ionization time\u2010of\u2010flight (<jats:styled-content style=\"fixed-case\">SELDI<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TOF<\/jats:styled-content>) mass spectrometry. Differences in peak intensity from <jats:styled-content style=\"fixed-case\">SELDI<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TOF<\/jats:styled-content> spectra were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Levels of 10 peaks were statistically significantly different between manifest gene\u2010expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo\u2010measure of disease severity (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.001), and the Symbol Digit Modalities Test (0.04) in manifest and <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content>\u2212age product score (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.019) in all gene\u2010expansion carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and relevance<\/jats:title><jats:p>Multiple studies have shown that the ubiquitin\u2010proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin\u2010proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content>\u2212age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.12750","type":"journal-article","created":{"date-parts":[[2015,6,13]],"date-time":"2015-06-13T08:08:01Z","timestamp":1434182881000},"page":"1378-1384","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease"],"prefix":"10.1111","volume":"22","author":[{"given":"T.","family":"Vinther\u2010Jensen","sequence":"first","affiliation":[{"name":"Department of Neurology Danish Dementia Research Centre Neurogenetics Clinic Rigshospitalet University of Copenhagen Copenhagen Denmark"},{"name":"Department of Cellular and Molecular Medicine Section\u00a0of Neurogenetics University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H.","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Department of Neurology Danish Dementia Research Centre Neurogenetics Clinic Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Budtz\u2010J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. E.","family":"Hjermind","sequence":"additional","affiliation":[{"name":"Department of Neurology Danish Dementia Research Centre Neurogenetics Clinic Rigshospitalet University of Copenhagen Copenhagen Denmark"},{"name":"Department of Cellular and Molecular Medicine Section\u00a0of Neurogenetics University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. E.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Neurology Danish Dementia Research Centre Neurogenetics Clinic Rigshospitalet University of Copenhagen Copenhagen Denmark"},{"name":"Department of Cellular and Molecular Medicine Section\u00a0of Neurogenetics University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-971176"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1990"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm312"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328304b692"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl027"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06022"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25835"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800231-MCP200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015809"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-014-0114-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31232"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.3.366"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.01.011"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600426"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/837015"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00218"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1886"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760600918142"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.12750","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.12750","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:24:46Z","timestamp":1695551086000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.12750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,13]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1111\/ene.12750"],"URL":"https:\/\/doi.org\/10.1111\/ene.12750","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"type":"print","value":"1351-5101"},{"type":"electronic","value":"1468-1331"}],"subject":[],"published":{"date-parts":[[2015,6,13]]},"assertion":[{"value":"2014-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}