| http://purl.uniprot.org/citations/26308891 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26308891 | http://www.w3.org/2000/01/rdf-schema#comment | "The hexanucleotide repeat expansion (HRE) GGGGCC (G4C2) in C9orf72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies support an HRE RNA gain-of-function mechanism of neurotoxicity, and we previously identified protein interactors for the G4C2 RNA including RanGAP1. A candidate-based genetic screen in Drosophila expressing 30 G4C2 repeats identified RanGAP (Drosophila orthologue of human RanGAP1), a key regulator of nucleocytoplasmic transport, as a potent suppressor of neurodegeneration. Enhancing nuclear import or suppressing nuclear export of proteins also suppresses neurodegeneration. RanGAP physically interacts with HRE RNA and is mislocalized in HRE-expressing flies, neurons from C9orf72 ALS patient-derived induced pluripotent stem cells (iPSC-derived neurons), and in C9orf72 ALS patient brain tissue. Nuclear import is impaired as a result of HRE expression in the fly model and in C9orf72 iPSC-derived neurons, and these deficits are rescued by small molecules and antisense oligonucleotides targeting the HRE G-quadruplexes. Nucleocytoplasmic transport defects may be a fundamental pathway for ALS and FTD that is amenable to pharmacotherapeutic intervention."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature14973"xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Gupta S."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Zhang K."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Rothstein J.D."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Huganir R.L."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Miller S.J."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Matunis M.J."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Thomas M.A."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Donnelly C.J."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Haeusler A.R."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Sattler R."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Lloyd T.E."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Ostrow L.W."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Vidensky S."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Cunningham K.M."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Chiu S.L."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Hong I."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Grima J.C."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Machamer J.B."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Daley E.L."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/author | "Steinwald P."xsd:string |
| http://purl.uniprot.org/citations/26308891 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |