| http://purl.uniprot.org/citations/17255335 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17255335 | http://www.w3.org/2000/01/rdf-schema#comment | "Reactive astrocytes and microglia in Alzheimer's disease surround amyloid plaques and secrete proinflammatory cytokines that affect neuronal function. Relationship between cytokine signaling and amyloid-beta peptide (Abeta) accumulation is poorly understood. Thus, we generated a novel Swedish beta-amyloid precursor protein mutant (APP) transgenic mouse in which the interferon (IFN)-gamma receptor type I was knocked out (APP/GRKO). IFN-gamma signaling loss in the APP/GRKO mice reduced gliosis and amyloid plaques at 14 months of age. Aggregated Abeta induced IFN-gamma production from co-culture of astrocytes and microglia, and IFN-gamma elicited tumor necrosis factor (TNF)-alpha secretion in wild type (WT) but not GRKO microglia co-cultured with astrocytes. Both IFN-gamma and TNF-alpha enhanced Abeta production from APP-expressing astrocytes and cortical neurons. TNF-alpha directly stimulated beta-site APP-cleaving enzyme (BACE1) expression and enhanced beta-processing of APP in astrocytes. The numbers of reactive astrocytes expressing BACE1 were increased in APP compared with APP/GRKO mice in both cortex and hippocampus. IFN-gamma and TNF-alpha activation of WT microglia suppressed Abeta degradation, whereas GRKO microglia had no changes. These results support the idea that glial IFN-gamma and TNF-alpha enhance Abeta deposition through BACE1 expression and suppression of Abeta clearance. Taken together, these observations suggest that proinflammatory cytokines are directly linked to Alzheimer's disease pathogenesis."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.org/dc/terms/identifier | "doi:10.2353/ajpath.2007.060378"xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/author | "Yamamoto M."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/author | "Gendelman H.E."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/author | "Horiba M."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/author | "Kiyota T."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/author | "Buescher J.L."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/author | "Ikezu T."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/author | "Walsh S.M."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/pages | "680-692"xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/title | "Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice."xsd:string |
| http://purl.uniprot.org/citations/17255335 | http://purl.uniprot.org/core/volume | "170"xsd:string |
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