| http://purl.uniprot.org/citations/22170863 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22170863 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22170863 | http://www.w3.org/2000/01/rdf-schema#comment | "A mutation in the BRI2/ITM2b gene causes loss of BRI2 protein leading to familial Danish dementia (FDD). BRI2 deficiency of FDD provokes an increase in amyloid-β precursor protein (APP) processing since BRI2 is an inhibitor of APP proteolysis, and APP mediates the synaptic/memory deficits in FDD. APP processing is linked to Alzheimer disease (AD) pathogenesis, which is consistent with a common mechanism involving toxic APP metabolites in both dementias. We show that inhibition of APP cleavage by β-secretase rescues synaptic/memory deficits in a mouse model of FDD. β-cleavage of APP yields amino-terminal-soluble APPβ (sAPPβ) and β-carboxyl-terminal fragments (β-CTF). Processing of β-CTF by γ-secretase releases amyloid-β (Aβ), which is assumed to cause AD. However, inhibition of γ-secretase did not ameliorate synaptic/memory deficits of FDD mice. These results suggest that sAPPβ and/or β-CTF, rather than Aβ, are the toxic species causing dementia, and indicate that reducing β-cleavage of APP is an appropriate therapeutic approach to treating human dementias. Our data and the failures of anti-Aβ therapies in humans advise against targeting γ-secretase cleavage of APP and/or Aβ."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.org/dc/terms/identifier | "doi:10.1002/emmm.201100195"xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.org/dc/terms/identifier | "doi:10.1002/emmm.201100195"xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "Matsuda S."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "Matsuda S."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "D'Adamio L."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "D'Adamio L."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "Arancio O."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "Arancio O."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "Tamayev R."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/author | "Tamayev R."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/name | "EMBO Mol. Med."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/name | "EMBO Mol. Med."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/pages | "171-179"xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/pages | "171-179"xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/title | "beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/title | "beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia."xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/volume | "4"xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://purl.uniprot.org/core/volume | "4"xsd:string |
| http://purl.uniprot.org/citations/22170863 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22170863 |
| http://purl.uniprot.org/citations/22170863 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22170863 |