{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:14:33Z","timestamp":1791918873065,"version":"4.3.4"},"reference-count":96,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2007,4,23]],"date-time":"2007-04-23T00:00:00Z","timestamp":1177286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disease caused by an abnormally expanded CAG repeat in the HD gene. Ubiquitylated aggregates containing mutant huntingtin protein in neurons are hallmarks of HD. Misfolded mutant huntingtin monomers, oligomers, or aggregates may be a result of, and cause, ubiquitin\u2010 proteasome dysfunction. To investigate the ubiquitin\u2010proteasome system we designed a series of firefly luciferase reporters targeted selectively to different points along this pathway. These reporters were used to monitor ubiquitin\u2010proteasome system function in a striatal cell culture model of HD. Ubiquitylation processes were not reduced in mutant huntingtin cells but recognition or degradation of ubiquitylated substrates was decreased. We also found mutant huntingtin expressing cells had slight but significant decreases in chymotrypsin\u2010like and caspase\u2010like activities, and an unexpected increase in trypsin\u2010like activity of the proteasome core. General proteasome core inhibitors, as well as selective caspase\u2010like activity inhibitors, were less effective in mutant cells. Finally, treatment with 3\u2010nitropropionic acid, a succinate dehydrogenase inhibitor, had opposite effects on the ubiquitin\u2010proteasome system with activation in wild\u2010type and decreased activity in mutant huntingtin expressing cells. The results of these experiments show clearly selective disruption of the ubiquitin\u2010proteasome system in this cell culture model of HD. The high throughput tools that we have designed and optimized will also be useful in identifying compounds that alter ubiquitin\u2010proteasome system function and to investigate other neurodegenerative diseases such Alzheimer's disease and Parkinson's disease. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21287","type":"journal-article","created":{"date-parts":[[2007,4,23]],"date-time":"2007-04-23T21:22:07Z","timestamp":1177363327000},"page":"1774-1788","source":"Crossref","is-referenced-by-count":45,"title":["Ubiquitin\u2010proteasome system alterations in a striatal cell model of huntington's disease"],"prefix":"10.1002","volume":"85","author":[{"given":"Jesse M.","family":"Hunter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Lesort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail 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