| http://purl.uniprot.org/citations/23468938 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23468938 | http://www.w3.org/2000/01/rdf-schema#comment | "Cytosolic aggregation of the nuclear RNA-binding protein TDP-43 is a histopathologic signature of degenerating neurons in amyotrophic lateral sclerosis (ALS), and mutations in the TARDBP gene encoding TDP-43 cause dominantly inherited forms of this condition. To understand the relationship between TDP-43 misregulation and neurotoxicity, we and others have used Drosophila as a model system, in which overexpression of either wild-type TDP-43 or its ALS-associated mutants in neurons is sufficient to induce neurotoxicity, paralysis, and early death. Using microarrays, we have examined gene expression patterns that accompany TDP-43-induced neurotoxicity in the fly system. Constitutive expression of TDP-43 in the Drosophila compound eye elicited widespread gene expression changes, with strong upregulation of cell cycle regulatory genes and genes functioning in the Notch intercellular communication pathway. Inducible expression of TDP-43 specifically in neurons elicited significant expression differences in a more restricted set of genes. Genes that were upregulated in both paradigms included SpindleB and the Notch target Hey, which appeared to be a direct TDP-43 target. Mutations that diminished activity of Notch or disrupted the function of downstream Notch target genes extended the lifespan of TDP-43 transgenic flies, suggesting that Notch activation was deleterious in this model. Finally, we showed that mutation of the nucleoporin Nup50 increased the lifespan of TDP-43 transgenic flies, suggesting that nuclear events contribute to TDP-43-dependent neurotoxicity. The combined findings identified pathways whose deregulation might contribute to TDP-43-induced neurotoxicity in Drosophila."xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0057214"xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/author | "Kim S.H."xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/author | "Zhan L."xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/author | "Tibbetts R.S."xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/author | "Hanson K.A."xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/author | "Tare A."xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/pages | "e57214"xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/title | "Identification of genetic modifiers of TDP-43 neurotoxicity in Drosophila."xsd:string |
| http://purl.uniprot.org/citations/23468938 | http://purl.uniprot.org/core/volume | "8"xsd:string |
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