| http://purl.uniprot.org/citations/23618906 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23618906 | http://www.w3.org/2000/01/rdf-schema#comment | "Aggregates of amyloid-beta (Aβ) and tau are hallmarks of Alzheimer's disease (AD) leading to neurodegeneration and synaptic loss. While increasing evidence suggests that inhibition of N-methyl-D-aspartate receptors (NMDARs) may mitigate certain aspects of AD neuropathology, the precise role of different NMDAR subtypes for Aβ- and tau-mediated toxicity remains to be elucidated. Using mouse organotypic hippocampal slice cultures from arcAβ transgenic mice combined with Sindbis virus-mediated expression of human wild-type tau protein (hTau), we show that Aβ caused dendritic spine loss independently of tau. However, the presence of hTau was required for Aβ-induced cell death accompanied by increased hTau phosphorylation. Inhibition of NR2B-containing NMDARs abolished Aβ-induced hTau phosphorylation and toxicity by preventing GSK-3β activation but did not affect dendritic spine loss. Inversely, NR2A-containing NMDAR inhibition as well as NR2A-subunit knockout diminished dendritic spine loss but not the Aβ effect on hTau. Activation of extrasynaptic NMDARs in primary neurons caused degeneration of hTau-expressing neurons, which could be prevented by NR2B-NMDAR inhibition but not by NR2A knockout. Furthermore, caspase-3 activity was increased in arcAβ transgenic cultures. Activity was reduced by NR2A knockout but not by NR2B inhibition. Accordingly, caspase-3 inhibition abolished spine loss but not hTau-dependent toxicity in arcAβ transgenic slice cultures. Our data show that Aβ induces dendritic spine loss via a pathway involving NR2A-containing NMDARs and active caspase-3 whereas activation of eSyn NR2B-containing NMDARs is required for hTau-dependent neurodegeneration, independent of caspase-3."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.org/dc/terms/identifier | "doi:10.1038/cddis.2013.129"xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Nitsch R.M."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Brandt R."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Konietzko U."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Grimm J."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Trutzel A."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Tackenberg C."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Frey M.C."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Grinschgl S."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/author | "Santuccione A.C."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/name | "Cell Death Dis"xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/pages | "e608"xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/title | "NMDA receptor subunit composition determines beta-amyloid-induced neurodegeneration and synaptic loss."xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://purl.uniprot.org/core/volume | "4"xsd:string |
| http://purl.uniprot.org/citations/23618906 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23618906 |
| http://purl.uniprot.org/citations/23618906 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23618906 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JEA7-mappedCitation-23618906 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23618906 |
| http://purl.uniprot.org/uniprot/#_G3X9V4-mappedCitation-23618906 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23618906 |
| http://purl.uniprot.org/uniprot/#_Q01097-mappedCitation-23618906 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23618906 |
| http://purl.uniprot.org/uniprot/#_P35436-mappedCitation-23618906 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23618906 |
| http://purl.uniprot.org/uniprot/#_Q3TR00-mappedCitation-23618906 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23618906 |
| http://purl.uniprot.org/uniprot/#_Q8CG67-mappedCitation-23618906 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23618906 |