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dc.contributor.authorROWAN, MICHAELen
dc.contributor.authorANWYL, ROGERen
dc.contributor.authorROWAN, MICHAEL JOSEPHen
dc.contributor.authorANWYL, ROGERen
dc.date.accessioned2015-12-09T12:41:18Z
dc.date.available2015-12-09T12:41:18Z
dc.date.issued2015en
dc.date.submitted2015en
dc.identifier.citationChang L, Cui W, Yang Y, Xu S, Zhou W, Fu H, Hu S, Mak S, Hu J, Wang Q, Pui-Yan Ma V, Chung-Lit Choi T, Dik-Lung Ma E, Tao L, Pang Y, Rowan M.J, Anwyl R, Han Y, Wang Q, Protection against ß-amyloid-induced synaptic and memory impairments via altering ß-amyloid assembly by bis(heptyl)-cognitin, Scientific Reports, 5, 2015, 10256-en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/75237
dc.descriptionPUBLISHEDen
dc.description.abstractβ-amyloid (Aβ) oligomers have been closely implicated in the pathogenesis of Alzheimer’s disease (AD). We found, for the first time, that bis(heptyl)-cognitin, a novel dimeric acetylcholinesterase (AChE) inhibitor derived from tacrine, prevented Aβ oligomers-induced inhibition of long-term potentiation (LTP) at concentrations that did not interfere with normal LTP. Bis(heptyl)-cognitin also prevented Aβ oligomers-induced synaptotoxicity in primary hippocampal neurons. In contrast, tacrine and donepezil, typical AChE inhibitors, could not prevent synaptic impairments in these models, indicating that the modification of Aβ oligomers toxicity by bis(heptyl)-cognitin might be attributed to a mechanism other than AChE inhibition. Studies by using dot blotting, immunoblotting, circular dichroism spectroscopy, and transmission electron microscopy have shown that bis(heptyl)-cognitin altered Aβ assembly via directly inhibiting Aβ oligomers formation and reducing the amount of preformed Aβ oligomers. Molecular docking analysis further suggested that bis(heptyl)-cognitin presumably interacted with the hydrophobic pockets of Aβ, which confers stabilizing powers and assembly alteration effects on Aβ. Most importantly, bis(heptyl)-cognitin significantly reduced cognitive impairments induced by intra-hippocampal infusion of Aβ oligomers in mice. These results clearly demonstrated how dimeric agents prevent Aβ oligomers-induced synaptic and memory impairments, and offered a strong support for the beneficial therapeutic effects of bis(heptyl)-cognitin in the treatment of AD.en
dc.description.sponsorshipThis work was supported by grants from the National Nature Science Foundation of China (81271209, 81471398), 973 program from the Ministry of Science and Technology of China (2013CB835100), the Research Grants Council of Hong Kong (561011, 15101014), The Hong Kong Polytechnic University (G-U952, G-YM32, G-SB10 and G-YZ15), Ningbo Key Science and Technology Project (2011C51006), the K.C. Wong Magna Fund in Ningbo University. We sincerely thank Ms. Josephine Leung for proofreading our manuscript. The authors declare no competing financial interests.en
dc.format.extent10256en
dc.relation.ispartofseriesScientific Reportsen
dc.relation.ispartofseries5en
dc.rightsYen
dc.subjectβ-amyloid (Aβ)en
dc.subject.lcshβ-amyloid (Aβ)en
dc.titleProtection against ß-amyloid-induced synaptic and memory impairments via altering ß-amyloid assembly by bis(heptyl)-cognitinen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mrowanen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ranwylen
dc.identifier.rssinternalid105753en
dc.identifier.doihttp://dx.doi.org/10.1038/srep10256en
dc.rights.ecaccessrightsopenAccess
dc.identifier.rssurihttp://www.scopus.com/inward/record.url?eid=2-s2.0-84937686037&partnerID=40&md5=ae4a4df538efff9245d0c276098d4ff9en


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