| http://purl.uniprot.org/citations/23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23980182 | http://www.w3.org/2000/01/rdf-schema#comment | "Huntington disease (HD) is a progressive neurodegenerative disorder caused by dominant polyglutamine (polyQ) expansion within the N terminus of huntingtin (Htt) protein. Abnormal metal accumulation in the striatum of HD patients has been reported for many years, but a causative relationship has not yet been established. Furthermore, if metal is indeed involved in HD, the underlying mechanism needs to be explored. Here using a Drosophila model of HD, wherein Htt exon1 with expanded polyQ (Htt exon1-polyQ) is introduced, we show that altered expression of genes involved in copper metabolism significantly modulates the HD progression. Intervention of dietary copper levels also modifies HD phenotypes in the fly. Copper reduction to a large extent decreases the level of oligomerized and aggregated Htt. Strikingly, substitution of two potential copper-binding residues of Htt, Met8 and His82, completely dissociates the copper-intensifying toxicity of Htt exon1-polyQ. Our results therefore indicate HD entails two levels of toxicity: the copper-facilitated protein aggregation as conferred by a direct copper binding in the exon1 and the copper-independent polyQ toxicity. The existence of these two parallel pathways converging into Htt toxicity also suggests that an ideal HD therapy would be a multipronged approach that takes both these actions into consideration."xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1308535110"xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/author | "Zhou B."xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/author | "Xiao G."xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/author | "Fan Q."xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/pages | "14995-15000"xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/title | "Huntington disease arises from a combinatory toxicity of polyglutamine and copper binding."xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://purl.uniprot.org/core/volume | "110"xsd:string |
| http://purl.uniprot.org/citations/23980182 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23980182 |
| http://purl.uniprot.org/citations/23980182 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23980182 |
| http://purl.uniprot.org/uniprot/#_A0A0B4KFM8-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_A0A0B4LHD1-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_A8K3C9-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTD2-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTD4-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTD5-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTD6-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTD7-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTD8-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTD9-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |
| http://purl.uniprot.org/uniprot/#_D2CTE1-mappedCitation-23980182 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23980182 |