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The disease is characterized by motor, behavioural and cognitive symptoms for which at present there are no disease altering treatments. It has been shown that manipulating the mTOR (mammalian target of rapamycin) pathway using rapamycin or its analogue CCI-779 can improve the cellular and behavioural phenotypes of HD models. Ribosomal protein S6 kinase 1 (S6K1) is a major downstream signalling molecule of mTOR, and its activity is reduced by rapamycin suggesting that deregulation of S6K1 activity may be beneficial in HD. Furthermore, <jats:italic>S6k1<\/jats:italic> knockout mice have increased lifespan and improvement in age-related phenotypes. To evalute the potential benefit of <jats:italic>S6k1<\/jats:italic> loss on HD-related phenotypes, we crossed the R6\/2 HD model with the long-lived <jats:italic>S6k1<\/jats:italic> knockout mouse line. We found that <jats:italic>S6k1<\/jats:italic> knockout does not ameliorate behavioural or physiological phenotypes in the R6\/2 mouse model. Additionally, no improvements were seen in brain mass reduction or mutant\u00a0huntingtin protein aggregate levels. Therefore, these results suggest that while a reduction in S6K1 signalling has beneficial effects on ageing it is unlikely to be a therapeutic strategy for HD patients.<\/jats:p>","DOI":"10.1038\/s41598-019-52391-3","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T11:03:34Z","timestamp":1573038214000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic deletion of S6k1 does not rescue the phenotypic deficits observed in the R6\/2 mouse model of Huntington\u2019s disease"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-8140","authenticated-orcid":false,"given":"Elaine E.","family":"Irvine","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-6116","authenticated-orcid":false,"given":"Loukia","family":"Katsouri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Plattner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hind","family":"Al-Qassab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rand","family":"Al-Nackkash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-6305","authenticated-orcid":false,"given":"Gillian P.","family":"Bates","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-7521","authenticated-orcid":false,"given":"Dominic J.","family":"Withers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,11,6]]},"reference":[{"key":"52391_CR1","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","volume":"72","author":"ME MacDonald","year":"1993","unstructured":"MacDonald, M. 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