| http://purl.uniprot.org/citations/32857910 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32857910 | http://www.w3.org/2000/01/rdf-schema#comment | "The cerebral amyloid-β accumulation that begins in middle age is considered the critical triggering event in the pathogenesis of late-onset Alzheimer's disease (LOAD). However, the molecular mechanism remains elusive. The Shugoshin 1 (Sgo1-/+ ) mouse model, a model for mitotic cohesinopathy-genomic instability that is observed in human AD at a higher rate, showed spontaneous accumulation of amyloid-β in the brain at old age. With the model, novel insights into the molecular mechanism of LOAD development are anticipated. In this study, the initial appearance of cerebral amyloid-β accumulation was determined as 15-18 months of age (late middle age) in the Sgo1-/+ model. The amyloid-β accumulation was associated with unexpected GSK3α/β inactivation, Wnt signaling activation, and ARC/Arg3.1 accumulation, suggesting involvement of both the GSK3-Arc/Arg3.1 axis and the GSK3-Wnt axis. As observed in human AD brains, neuroinflammation with IFN-γ expression occurred with amyloid-β accumulation and was pronounced in the aged (24-month-old) Sgo1-/+ model mice. AD-relevant protein panels (oxidative stress defense, mitochondrial energy metabolism, and β-oxidation and peroxisome) analysis indicated (a) early increases in Pdk1 and Phb in middle-aged Sgo1-/+ brains, and (b) misregulations in 32 proteins among 130 proteins tested in old age. Thus, initial amyloid-β accumulation in the Sgo1-/+ model is suggested to be triggered by GSK3 inactivation and the resulting Wnt activation and ARC/Arg3.1 accumulation. The model displayed characteristics and affected pathways similar to those of human LOAD including neuroinflammation, demonstrating its potential as a study tool for the LOAD development mechanism and for preclinical AD drug research and development."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.org/dc/terms/identifier | "doi:10.1111/acel.13221"xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/author | "Rao C.V."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/author | "Yamada H.Y."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/author | "Asch A.S."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/author | "Farooqui M."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/author | "Madhavaram A."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/name | "Aging Cell"xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/pages | "e13221"xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/title | "GSK3-ARC/Arg3.1 and GSK3-Wnt signaling axes trigger amyloid-beta accumulation and neuroinflammation in middle-aged Shugoshin 1 mice."xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://purl.uniprot.org/core/volume | "19"xsd:string |
| http://purl.uniprot.org/citations/32857910 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32857910 |
| http://purl.uniprot.org/citations/32857910 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32857910 |
| http://purl.uniprot.org/uniprot/#_Q9CXH7-mappedCitation-32857910 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32857910 |
| http://purl.uniprot.org/uniprot/Q9CXH7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32857910 |