| http://purl.uniprot.org/citations/24548080 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24548080 | http://www.w3.org/2000/01/rdf-schema#comment | "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-specific proteins. In case of SCA3, mutation of Ataxin-3 results in aggregation of misfolded protein, formation of intranuclear as well as cytosolic inclusion bodies and cell death in distinct neuronal populations. Since cyclin-dependent kinase-5 (CDK5) has been shown to exert beneficial effects on aggregate formation and cell death in various polyglutamine diseases, we tested its therapeutic potential for SCA3. Our data show increased caspase-dependent Ataxin-3 cleavage, aggregation, and neurodegeneration in the absence of sufficient CDK5 activity. This disease-propagating effect could be reversed by mutation of the caspase cleavage site in Ataxin-3. Moreover, reduction of CDK5 expression levels by RNAi in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. In summary, we present CDK5 as a potent neuroprotectant, regulating cleavage and thereby toxicity of Ataxin-3 and other polyglutamine proteins. We propose that increased caspase-dependent cleavage of mutated Ataxin-3, because of missing CDK5 shielding, leads to aggregation and cell death. Moreover, reduction of CDK5 expression levels by RNAi in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. We think that CDK5 functions as a shield against cleavage-induced toxification and thereby is an interesting target for therapeutic intervention in polyQ disease in general."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.org/dc/terms/identifier | "doi:10.1111/jnc.12684"xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Voigt A."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Kermer P."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Schulz J.B."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Bahr M."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Deeg S."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Dohm C.P."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Liman J."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Weishaupt J."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Karch A."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/author | "Vossfeldt H."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/name | "J Neurochem"xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/pages | "1013-1023"xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/title | "CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration."xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://purl.uniprot.org/core/volume | "129"xsd:string |
| http://purl.uniprot.org/citations/24548080 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24548080 |
| http://purl.uniprot.org/citations/24548080 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24548080 |
| http://purl.uniprot.org/uniprot/P54252#attribution-9E38328427310ADC9E99FE4114F88C7E | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/24548080 |
| http://purl.uniprot.org/uniprot/P29466#attribution-9E38328427310ADC9E99FE4114F88C7E | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/24548080 |
| http://purl.uniprot.org/uniprot/Q00535#attribution-69DEDC7D8442898607F24592B624A001 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/24548080 |
| http://purl.uniprot.org/uniprot/#_P10090-mappedCitation-24548080 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24548080 |
| http://purl.uniprot.org/uniprot/#_P48609-mappedCitation-24548080 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24548080 |