| http://purl.uniprot.org/citations/34018922 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34018922 | http://www.w3.org/2000/01/rdf-schema#comment | "Neurofibrillary tangles composed of hyperphosphorylated tau and synaptic dysfunction are characteristics of Alzheimer's disease (AD). However, the underlying molecular mechanisms remain poorly understood. Here, we identified Amphiphysin I mediates both tau phosphorylation and synaptic dysfunction in AD. Amphiphysin I is cleaved by a cysteine proteinase asparagine endopeptidase (AEP) at N278 in the brains of AD patients. The amount of AEP-generated N-terminal fragment of Amphiphysin I (1-278) is increased with aging. Amphiphysin I (1-278) inhibits clathrin-mediated endocytosis and induces synaptic dysfunction. Furthermore, Amphiphysin I (1-278) binds p35 and promotes its transition to p25, thus activates CDK5 and enhances tau hyperphosphorylation. Overexpression of Amphiphysin I (1-278) in the hippocampus of Tau P301S mice induces synaptic dysfunction, tau hyperphosphorylation, and cognitive deficits. However, overexpression of the N278A mutant Amphiphysin I, which resists the AEP-mediated cleavage, alleviates the pathological and behavioral defects. These findings suggest a mechanism of tau hyperphosphorylation and synaptic dysfunction in AD."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.org/dc/terms/identifier | "doi:10.7554/elife.65301"xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Chen G."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Cao X."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Pan L."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Tang L."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Zhang Z."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Zheng Y."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Wang Z."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Wang T."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Zhang Z.'"xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Ye K."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Xiong J."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Zou L."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Xiong M."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Meng L."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/author | "Duong D.M."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/name | "Elife"xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/pages | "e65301"xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/title | "Amphiphysin I cleavage by asparagine endopeptidase leads to tau hyperphosphorylation and synaptic dysfunction."xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/34018922 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34018922 |