{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:58:27Z","timestamp":1787065107466,"version":"build-2736575974"},"reference-count":15,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Exp Neurosci"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Huntington\u2019s disease (HD) is a monogenic fatal neurodegenerative disorder. However, there is increasing evidence that HD is a pleiotropic systemic disorder. In particular, skeletal muscle metabolism is greatly affected in HD, which in turn can have a major impact on whole-body metabolism and energetic balance. Throughout an unbiased mutagenesis approach in HD mice, we have found that Scn4a, a skeletal muscle\u2013specific sodium channel gene, is a modifier of the disease. Mutations in Scn4a enhance HD disease progression and weight loss by accelerating muscle waste and cachexia, increasing skeletal muscle activity and energy demands. At the molecular level, Scn4a mutations activate AMP-activated protein kinase (AMPK), leading to a fibre switch towards more oxidative types. These adaptations seen in HD; Scn4a double mutant muscles are similar to those observed in healthy individuals after endurance exercise training regimes. This prompted us to assess the effects of an endurance exercise regime in HD mice, independently showing that skeletal muscle adaptations leading to the activation of AMPK are detrimental for HD pathogenesis. Although it is undeniable that physical exercise can lead to many health benefits, our work shows that, at least under certain situations such as in HD, an endurance exercise routine could be a detrimental therapeutic option.<\/jats:p>","DOI":"10.1177\/1179069518809059","type":"journal-article","created":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T08:16:42Z","timestamp":1540887402000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Skeletal Muscle Modulates Huntington\u2019s Disease Pathogenesis in Mice: Role of Physical Exercise"],"prefix":"10.1177","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0958-0083","authenticated-orcid":false,"given":"Silvia","family":"Corrochano","sequence":"first","affiliation":[{"name":"Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Blanco","sequence":"additional","affiliation":[{"name":"Department of Biology, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Acevedo-Arozena","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n, Hospital Universitario de Canarias, Fundaci\u00f3n Canaria de Investigaci\u00f3n Sanitaria e Instituto de Tecnolog\u00edas Biom\u00e9dicas, La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,10,30]]},"reference":[{"key":"bibr1-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200001)47:1<64::AID-ANA11>3.0.CO;2-S"},{"key":"bibr2-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318275df4b"},{"key":"bibr3-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.10.004"},{"key":"bibr4-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.010"},{"key":"bibr5-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.015"},{"key":"bibr6-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2015.09.005"},{"key":"bibr7-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.03.019"},{"key":"bibr8-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-6-51"},{"key":"bibr9-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-236331"},{"key":"bibr10-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy077"},{"key":"bibr11-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8310-1"},{"key":"bibr12-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.07.014"},{"key":"bibr13-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1201"},{"key":"bibr14-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv513"},{"key":"bibr15-1179069518809059","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201105010"}],"container-title":["Journal of Experimental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1179069518809059","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1179069518809059","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1179069518809059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T21:03:23Z","timestamp":1777410203000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1179069518809059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":15,"alternative-id":["10.1177\/1179069518809059"],"URL":"https:\/\/doi.org\/10.1177\/1179069518809059","relation":{},"ISSN":["1179-0695","1179-0695"],"issn-type":[{"value":"1179-0695","type":"print"},{"value":"1179-0695","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]},"article-number":"1179069518809059"}}