| http://purl.uniprot.org/citations/32913125 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32913125 | http://www.w3.org/2000/01/rdf-schema#comment | "Several plant-derived compounds have demonstrated efficacy in pre-clinical Alzheimer's disease (AD) rodent models. Each of these compounds share a gallic acid (GA) moiety, and initial assays on this isolated molecule indicated that it might be responsible for the therapeutic benefits observed. To test this hypothesis in a more physiologically relevant setting, we investigated the effect of GA in the mutant human amyloid β-protein precursor/presenilin 1 (APP/PS1) transgenic AD mouse model. Beginning at 12 months, we orally administered GA (20 mg/kg) or vehicle once daily for 6 months to APP/PS1 mice that have accelerated Alzheimer-like pathology. At 18 months of age, GA therapy reversed impaired learning and memory as compared with vehicle, and did not alter behavior in nontransgenic littermates. GA-treated APP/PS1 mice had mitigated cerebral amyloidosis, including brain parenchymal and cerebral vascular β-amyloid deposits, and decreased cerebral amyloid β-proteins. Beneficial effects co-occurred with reduced amyloidogenic and elevated nonamyloidogenic APP processing. Furthermore, brain inflammation, gliosis, and oxidative stress were alleviated. We show that GA simultaneously elevates α- and reduces β-secretase activity, inhibits neuroinflammation, and stabilizes brain oxidative stress in a pre-clinical mouse model of AD. We further demonstrate that GA increases abundance of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10, Adam10) proprotein convertase furin and activates ADAM10, directly inhibits β-site APP cleaving enzyme 1 (BACE1, Bace1) activity but does not alter Adam10 or Bace1 transcription. Thus, our data reveal novel post-translational mechanisms for GA. We suggest further examination of GA supplementation in humans will shed light on the exciting therapeutic potential of this molecule."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra119.012330"xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Mori T."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Tan J."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Maeda M."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Koyama N."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Segawa T."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Yokoo T."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Town T."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/author | "Sawmiller D."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/pages | "16251-16266"xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/title | "Gallic acid is a dual alpha/beta-secretase modulator that reverses cognitive impairment and remediates pathology in Alzheimer mice."xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://purl.uniprot.org/core/volume | "295"xsd:string |
| http://purl.uniprot.org/citations/32913125 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32913125 |
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