| http://purl.uniprot.org/citations/37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37822142 | http://www.w3.org/2000/01/rdf-schema#comment | "Amyloid-β (Aβ) and hyper-phosphorylated tau are key hallmarks of Alzheimer's disease (AD), with an accumulation of both proteins linked to hippocampal synaptic dysfunction. Recent evidence indicates that Aβ drives mis-localisation of tau from axons to synapses, resulting in AMPA receptor (AMPAR) internalisation and impaired excitatory synaptic function. These tau-driven synaptic impairments are thought to underlie the cognitive deficits in AD. Consequently, limiting the synapto-toxic effects of tau may prevent AD-related cognitive deficits. Increasing evidence links leptin dysfunction with higher AD risk, and numerous studies have identified neuroprotective properties of leptin in AD models of Aβ-induced toxicity. However, it is unclear if leptin protects against tau-related synaptic dysfunction. Here we show that Aβ1-42 significantly increases dendritic and synaptic levels of tau and p-tau in hippocampal neurons, and these effects were blocked by leptin. In accordance with GSK-3β being involved in tau phosphorylation, the protective effects of leptin involve PI 3-kinase (PI3K) activation and inhibition of GSK-3β. Aβ1-42 -driven synaptic targeting of tau was associated with the removal of GluA1-containing AMPARs from synapses, which was also inhibited by leptin-driven inhibition of GSK-3β. Direct application of oligomeric tau to hippocampal neurons caused internalisation of GluA1-containing AMPARs and this effect was blocked by prior application of leptin. Similarly, leptin prevented the ability of tau to block induction of activity-dependent long-term potentiation (LTP) at hippocampal SC-CA1 synapses. These findings increase our understanding of the neuroprotective actions of leptin in the early pre-clinical stages of AD and further validate the leptin system as a therapeutic target in AD."xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.org/dc/terms/identifier | "doi:10.1111/jnc.15980"xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/author | "Hamilton K."xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/author | "Morrow K."xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/author | "Harvey J."xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/author | "Markantoni E."xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/name | "J Neurochem"xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/pages | "520-537"xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/title | "Leptin prevents aberrant targeting of tau to hippocampal synapses via PI 3 kinase driven inhibition of GSK3beta."xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://purl.uniprot.org/core/volume | "167"xsd:string |
| http://purl.uniprot.org/citations/37822142 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37822142 |
| http://purl.uniprot.org/citations/37822142 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37822142 |
| http://purl.uniprot.org/uniprot/#_B2R8Y2-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
| http://purl.uniprot.org/uniprot/#_B4DDB5-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
| http://purl.uniprot.org/uniprot/#_A4D0Y8-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
| http://purl.uniprot.org/uniprot/#_B4DXY2-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
| http://purl.uniprot.org/uniprot/#_D3HIE0-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
| http://purl.uniprot.org/uniprot/#_P41159-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
| http://purl.uniprot.org/uniprot/#_P35269-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
| http://purl.uniprot.org/uniprot/#_Q4TVR7-mappedCitation-37822142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37822142 |
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