{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:38:28Z","timestamp":1790674708370,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2018,7,7]],"date-time":"2018-07-07T00:00:00Z","timestamp":1530921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005277","name":"Presbyterian Historical Society","doi-asserted-by":"publisher","award":["NS41574"],"award-info":[{"award-number":["NS41574"]}],"id":[{"id":"10.13039\/100005277","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001671","name":"Hereditary Disease Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001671","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>Huntington's disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) is an autosomal dominant neurodegenerative disease which has no effective treatment and is characterized by psychiatric disorders, motor alterations, and dementia, with the cognitive deficits representing a devastating aspect of the disorder. Oxidative stress and elevated levels of lipid peroxidation (<jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content>) products are found in mouse models and patients with <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>, suggesting that strategies to reduce <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content> may be beneficial in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>. In contrast with traditional antioxidants, substituting hydrogen with deuterium at bis\u2010allylic sites in polyunsaturated fatty acids (D\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content>) decreases the rate\u2010limiting initiation step of <jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content> autoxidation, a strategy that has shown benefits in other neurodegenerative diseases. Here, we investigated the effect of D\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content> treatment in a knock\u2010in mouse model of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> (Q140) which presents motor deficits and neuropathology from a few months of age, and progressive cognitive decline. Q140 knock\u2010in mice were fed a diet containing either D\u2010 or H\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content>s for 5 months starting at 1 month of age. D\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content> treatment significantly decreased F<jats:sub>2<\/jats:sub>\u2010isoprostanes in the striatum by approximately 80% as compared to H\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content> treatment and improved performance in novel object recognition tests, without significantly changing motor deficits or huntingtin aggregation. Therefore, D\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content> administration represents a promising new strategy to broadly reduce rates of <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content>, and may be useful in improving a subset of the core deficits in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/febs.14590","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T16:49:54Z","timestamp":1529686194000},"page":"3002-3012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Deuterium\u2010reinforced linoleic acid lowers lipid peroxidation and mitigates cognitive impairment in the Q140 knock in mouse model of Huntington's disease"],"prefix":"10.1111","volume":"285","author":[{"given":"Asa","family":"Hatami","sequence":"first","affiliation":[{"name":"Department of Neurology the David Geffen School of Medicine University of California, Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunni","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology the David Geffen School of Medicine University of California, Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aroa","family":"Rela\u00f1o\u2010Gines","sequence":"additional","affiliation":[{"name":"Department of Neurology the David Geffen School of Medicine University of California, Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Neurology the David Geffen School of Medicine University of California, Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpine","family":"Galstyan","sequence":"additional","affiliation":[{"name":"Department of Neurology the David Geffen School of Medicine University of California, Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Neurology the David Geffen School of Medicine University of California, Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginger","family":"Milne","sequence":"additional","affiliation":[{"name":"Vanderbilt Division of Clinical Pharmacology Vanderbilt University Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Cantor","sequence":"additional","affiliation":[{"name":"Retrotope, Inc. 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