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It is caused by the expansion of a polyglutamine (polyQ) tract in the ataxin\u20103 protein. Nuclear localization of the affected protein is a key event in the pathology of <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3 via affecting nuclear organization, transcriptional dysfunction, and seeding aggregations, finally causing neurodegeneration and cell death. So far, there is no effective therapy to prevent or slow the progression of <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we explored the effect of divalproex sodium as an <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>i in <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3 cell models and explored how divalproex sodium interferes with pathogenetic processes causing <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that divalproex sodium rescues the hypoacetylation levels of histone H3 and attenuates cellular cytotoxicity induced by expanded ataxin\u20103 partly via preventing nuclear transport of ataxin\u20103 (particularly heat shock\u2010dependent).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study provides novel insights into the mechanisms of action of divalproex sodium as a possible treatment for <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3, beyond the known regulation of transcription.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12795","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T13:58:40Z","timestamp":1515592720000},"page":"404-411","source":"Crossref","is-referenced-by-count":19,"title":["Divalproex sodium modulates nuclear localization of ataxin\u20103 and prevents cellular toxicity caused by expanded ataxin\u20103"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3185-7432","authenticated-orcid":false,"given":"Zi\u2010Jian","family":"Wang","sequence":"first","affiliation":[{"name":"Genetic Engineering Laboratory, College of Biological and Environmental Engineering Xi'an University  Xi'an, Shaanxi China"},{"name":"Institute of Medical Genetics &amp; Applied Genomics 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