| http://purl.uniprot.org/citations/20731760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20731760 | http://www.w3.org/2000/01/rdf-schema#comment | "Null mutations in progranulin (GRN) are associated with frontotemporal lobar degeneration characterized by intraneuronal accumulation of TAR DNA-binding protein-43 (TDP-43). However, the mechanism by which GRN deficiency leads to neurodegeneration remains largely unknown. In primary cortical neurons derived from Grn knockout (Grn(-/-) ) mice, we found that Grn-deficiency causes significantly reduced neuronal survival and increased caspase-mediated apoptosis, which was not observed in primary mouse embryonic fibroblasts derived from Grn(-/-) mice. Also, neurons derived from Grn(-/-) mice showed an increased amount of pTDP-43 accumulations. Furthermore, proteasomal inhibition with MG132 caused increased caspase-mediated TDP-43 fragmentation and accumulation of detergent-insoluble 35- and 25-kDa C-terminal fragments in Grn(-/-) neurons and mouse embryonic fibroblasts. Interestingly, full-length TDP-43 also accumulated in the detergent-insoluble fraction, and caspase-inhibition prevented MG132-induced generation of TDP-43 C-terminal fragments but did not block the pathological conversion of full-length TDP-43 from soluble to insoluble species. These data suggest that GRN functions as a survival factor for cortical neurons and GRN-deficiency causes increased susceptibility to cellular stress. This leads to increased aggregation and accumulation of full-length TDP-43 along with its C-terminal derivatives by both caspase-dependent and independent mechanisms."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1471-4159.2010.06961.x"xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/author | "Kumar-Singh S."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/author | "Van Broeckhoven C."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/author | "Kleinberger G."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/author | "Timmermans J.P."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/author | "Ponsaerts P."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/author | "Wils H."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/author | "Joris G."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/name | "J Neurochem"xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/pages | "735-747"xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/title | "Increased caspase activation and decreased TDP-43 solubility in progranulin knockout cortical cultures."xsd:string |
| http://purl.uniprot.org/citations/20731760 | http://purl.uniprot.org/core/volume | "115"xsd:string |
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