| http://purl.uniprot.org/citations/19074461 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19074461 | http://www.w3.org/2000/01/rdf-schema#comment | "Hyperphosphorylation and aggregation of the microtubule-binding protein tau characterize a diverse array of neurodegenerative disorders. Most of these lack mutations in the encoding MAPT gene, and the role of tau in disease pathogenesis remains controversial. Among these tauopathies is Niemann-Pick type C disease (NPC), a lysosomal storage disorder characterized by progressive neurodegeneration and premature death, most often caused by an inherited deficiency in the intracellular lipid trafficking protein NPC1. To determine the extent to which tau affects NPC pathogenesis, we generated Npc1-/-mice deficient in tau. Unexpectedly, NPC1/tau double null mutants are generated in markedly smaller litters, exhibit an enhanced systemic phenotype and die significantly earlier than NPC1 single null mutants. As autophagy is up-regulated in NPC and protein degradation through this pathway depends on movement along microtubules, we knocked down MAPT expression in NPC1-deficient human fibroblasts and examined effects on this pathway. We show that an acute reduction of tau expression in a cellular model of NPC decreases induction and flux through the autophagic pathway. Our data establish that MAPT deletion exacerbates the NPC phenotype through a mechanism independent of tau protein aggregation and identifies a critical role for tau in the regulation of autophagy in NPC1-deficient cells."xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddn423"xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/author | "Elrick M.J."xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/author | "Lieberman A.P."xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/author | "Pacheco C.D."xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/pages | "956-965"xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/title | "Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis."xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://purl.uniprot.org/core/volume | "18"xsd:string |
| http://purl.uniprot.org/citations/19074461 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19074461 |
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