{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:31:53Z","timestamp":1790764313655,"version":"4.1.0"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:p>HD (Huntington's disease) is caused by a polyQ (polyglutamine) expansion in the huntingtin protein, which leads to protein misfolding and aggregation of this protein. Abnormal copper accumulation in the HD brain was first reported more than 15\u00a0years ago. Recent findings show that copper-regulatory genes are induced during HD and copper binds to an N-terminal fragment of huntingtin, supporting the involvement of abnormal copper metabolism in HD. We have demonstrated that in vitro copper accelerates the fibrillization of an N-terminal fragment of huntingtin with an expanded polyQ stretch (httExon1). As we found that copper also increases polyQ aggregation and toxicity in mammalian cells expressing httExon1, we investigated further whether overexpression of genes involved in copper metabolism, notably MTs (metallothioneins) known to bind copper, protect against httExon1 toxicity. Using a yeast model of HD, we have shown that overexpression of several genes involved in copper metabolism reduces polyQ-mediated toxicity. Overexpression of MT-3 in mammalian cells significantly reduced polyQ aggregation and toxicity. We propose that copper-binding and\/or -chaperoning proteins, especially MTs, are potential therapeutic targets for HD.<\/jats:p>","DOI":"10.1042\/bst0380552","type":"journal-article","created":{"date-parts":[[2010,3,24]],"date-time":"2010-03-24T14:16:27Z","timestamp":1269440187000},"page":"552-558","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington's disease"],"prefix":"10.1042","volume":"38","author":[{"given":"Sarah\u00a0L.","family":"Hands","sequence":"first","affiliation":[{"name":"Neuroscience Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Leicester, Adrian Building, University Road, Leicester LE1 7RH, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u00a0Umar","family":"Sajjad","sequence":"additional","affiliation":[{"name":"Neuroscience Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviano","family":"Giorgini","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Leicester, Adrian Building, University Road, Leicester LE1 7RH, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wyttenbach","sequence":"additional","affiliation":[{"name":"Neuroscience Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,3,22]]},"reference":[{"key":"2021111720534671300_B1","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain","volume":"277","author":"DiFiglia","year":"1997","journal-title":"Science"},{"key":"2021111720534671300_B2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.bbagrm.2008.05.008","article-title":"Polyglutamine gene function and dysfunction in the ageing brain","volume":"1779","author":"Hands","year":"2008","journal-title":"Biochim. 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