{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:37Z","timestamp":1791919057178,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,3,24]],"date-time":"2014-03-24T00:00:00Z","timestamp":1395619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"CMPB"},{"name":"Fritz-Thyssen-Foundation"},{"DOI":"10.13039\/100002243","name":"National Ataxia Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"crossref"}]},{"name":"KNDD","award":["01GI0703"],"award-info":[{"award-number":["01GI0703"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinocerebellar ataxia type 3 (SCA3) is one of at least nine inherited neurodegenerative diseases caused by an expansion of a polyglutamine tract within corresponding disease\u2010specific proteins. In case of <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3, mutation of Ataxin\u20103 results in aggregation of misfolded protein, formation of intranuclear as well as cytosolic inclusion bodies and cell death in distinct neuronal populations. Since cyclin\u2010dependent kinase\u20105 (<jats:styled-content style=\"fixed-case\">CDK<\/jats:styled-content>5) has been shown to exert beneficial effects on aggregate formation and cell death in various polyglutamine diseases, we tested its therapeutic potential for <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3. Our data show increased caspase\u2010dependent Ataxin\u20103 cleavage, aggregation, and neurodegeneration in the absence of sufficient <jats:styled-content style=\"fixed-case\">CDK<\/jats:styled-content>5 activity. This disease\u2010propagating effect could be reversed by mutation of the caspase cleavage site in Ataxin\u20103. Moreover, reduction of <jats:styled-content style=\"fixed-case\">CDK<\/jats:styled-content>5 expression levels by <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>i <jats:italic>in vivo<\/jats:italic> enhances <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3 toxicity as assayed in a <jats:italic>Drosophila<\/jats:italic> model for <jats:styled-content style=\"fixed-case\">SCA<\/jats:styled-content>3. In summary, we present <jats:styled-content style=\"fixed-case\">CDK<\/jats:styled-content>5 as a potent neuroprotectant, regulating cleavage and thereby toxicity of Ataxin\u20103 and other polyglutamine proteins.<\/jats:p><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12684-fig-0010-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>We propose that increased caspase\u2010dependent cleavage of mutated Ataxin\u20103, because of missing CDK5 shielding, leads to aggregation and cell death. Moreover, reduction of CDK5 expression levels by RNAi <jats:italic>in vivo<\/jats:italic> enhances SCA3 toxicity as assayed in a <jats:italic>Drosophila<\/jats:italic> model for SCA3. We think that CDK5 functions as a shield against cleavage\u2010induced toxification and thereby is an interesting target for therapeutic intervention in polyQ disease in general.<\/jats:p>","DOI":"10.1111\/jnc.12684","type":"journal-article","created":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T17:41:09Z","timestamp":1392745269000},"page":"1013-1023","source":"Crossref","is-referenced-by-count":22,"title":["<scp>CDK<\/scp>5 protects from caspase\u2010induced Ataxin\u20103 cleavage and neurodegeneration"],"prefix":"10.1111","volume":"129","author":[{"given":"Jan","family":"Liman","sequence":"first","affiliation":[{"name":"Department of Neurology University of G\u00f6ttingen G\u00f6ttingen Germany"},{"name":"Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Deeg","sequence":"additional","affiliation":[{"name":"Department of Neurology 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