| http://purl.uniprot.org/citations/25155018 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25155018 | http://www.w3.org/2000/01/rdf-schema#comment | "Frontotemporal dementia (FTD) is the most common cause of dementia in people under 60 yr of age and is pathologically associated with mislocalization of TAR DNA/RNA binding protein 43 (TDP-43) in approximately half of cases (FLTD-TDP). Mutations in the gene encoding progranulin (GRN), which lead to reduced progranulin levels, are a significant cause of familial FTLD-TDP. Grn-KO mice were developed as an FTLD model, but lack cortical TDP-43 mislocalization and neurodegeneration. Here, we report retinal thinning as an early disease phenotype in humans with GRN mutations that precedes dementia onset and an age-dependent retinal neurodegenerative phenotype in Grn-KO mice. Retinal neuron loss in Grn-KO mice is preceded by nuclear depletion of TDP-43 and accompanied by reduced expression of the small GTPase Ran, which is a master regulator of nuclear import required for nuclear localization of TDP-43. In addition, TDP-43 regulates Ran expression, likely via binding to its 3'-UTR. Augmented expression of Ran in progranulin-deficient neurons restores nuclear TDP-43 levels and improves their survival. Our findings establish retinal neurodegeneration as a new phenotype in progranulin-deficient FTLD, and suggest a pathological loop involving reciprocal loss of Ran and nuclear TDP-43 as an underlying mechanism."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.org/dc/terms/identifier | "doi:10.1084/jem.20140214"xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Chen R."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Gan L."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Yu G."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Ward M.E."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Green A."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Herz J."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Miller B.L."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Farese R.V. Jr."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Minami S."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Roberson E.D."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Seeley W.W."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Kraft T.W."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Martens L.H."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Sephton C.F."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Filiano A.J."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Gelfand J.M."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Arrant A.E."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Boscardin J."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/author | "Taubes A."xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/name | "J Exp Med"xsd:string |
| http://purl.uniprot.org/citations/25155018 | http://purl.uniprot.org/core/pages | "1937-1945"xsd:string |