| http://purl.uniprot.org/citations/26468204 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26468204 | http://www.w3.org/2000/01/rdf-schema#comment | "Aging is the most important risk factor associated with Alzheimer's disease (AD); however, the molecular mechanisms linking aging to AD remain unclear. Suppression of the ribosomal protein S6 kinase 1 (S6K1) increases healthspan and lifespan in several organisms, from nematodes to mammals. Here we show that S6K1 expression is upregulated in the brains of AD patients. Using a mouse model of AD, we found that genetic reduction of S6K1 improved synaptic plasticity and spatial memory deficits, and reduced the accumulation of amyloid-β and tau, the two neuropathological hallmarks of AD. Mechanistically, these changes were linked to reduced translation of tau and the β-site amyloid precursor protein cleaving enzyme 1, a key enzyme in the generation of amyloid-β. Our results implicate S6K1 dysregulation as a previously unidentified molecular mechanism underlying synaptic and memory deficits in AD. These findings further suggest that therapeutic manipulation of S6K1 could be a valid approach to mitigate AD pathology.Significance statementAging is the most important risk factor for Alzheimer's disease (AD). However, little is known about how it contributes to AD pathogenesis. S6 kinase 1 (S6K1) is a protein kinase involved in regulation of protein translation. Reducing S6K1 activity increases lifespan and healthspan. We report the novel finding that reducing S6K1 activity in 3xTg-AD mice ameliorates synaptic and cognitive deficits. These improvement were associated with a reduction in amyloid-β and tau pathology. Mechanistically, lowering S6K1 levels reduced translation of β-site amyloid precursor protein cleaving enzyme 1 and tau, two key proteins involved in AD pathogenesis. These data suggest that S6K1 may represent a molecular link between aging and AD. Given that aging is the most important risk factor for most neurodegenerative diseases, our results may have far-reaching implications into other diseases."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.2781-15.2015"xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Ma L."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Huang Z."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Wu J."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Turner D."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Messina A."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Branca C."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Talboom J.S."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Shaw D.M."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Oddo S."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/author | "Caccamo A."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/pages | "14042-14056"xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/title | "Reducing Ribosomal Protein S6 Kinase 1 Expression Improves Spatial Memory and Synaptic Plasticity in a Mouse Model of Alzheimer's Disease."xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://purl.uniprot.org/core/volume | "35"xsd:string |
| http://purl.uniprot.org/citations/26468204 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26468204 |
| http://purl.uniprot.org/citations/26468204 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26468204 |
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| http://purl.uniprot.org/uniprot/#_Q5SWG2-mappedCitation-26468204 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26468204 |
| http://purl.uniprot.org/uniprot/#_P23443-mappedCitation-26468204 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26468204 |
| http://purl.uniprot.org/uniprot/#_Q3UXD8-mappedCitation-26468204 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26468204 |