DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kam, Tae-In | ko |
dc.contributor.author | Park, Hyejin | ko |
dc.contributor.author | Gwon, Youngdae | ko |
dc.contributor.author | Song, Sungmin | ko |
dc.contributor.author | Kim, Seo-Hyun | ko |
dc.contributor.author | Moon, Seo Won | ko |
dc.contributor.author | Jo, Dong-Gyu | ko |
dc.contributor.author | Jung, Yong-Keun | ko |
dc.date.accessioned | 2023-03-10T09:01:02Z | - |
dc.date.available | 2023-03-10T09:01:02Z | - |
dc.date.created | 2023-03-10 | - |
dc.date.created | 2023-03-10 | - |
dc.date.created | 2023-03-10 | - |
dc.date.created | 2023-03-10 | - |
dc.date.issued | 2016-11 | - |
dc.identifier.citation | ELIFE, v.5 | - |
dc.identifier.issn | 2050-084X | - |
dc.identifier.uri | http://hdl.handle.net/10203/305553 | - |
dc.description.abstract | Amyloid-beta (A beta)-containing extracellular plaques and hyperphosphorylated tau-loaded intracellular neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease (AD). Although A beta exerts neuropathogenic activity through tau, the mechanistic link between A beta and tau pathology remains unknown. Here, we showed that the Fc gamma RIIb-SHIP2 axis is critical in A beta(1-42)-induced tau pathology. Fc gamma RIIb knockout or antagonistic Fc?RIIb antibody inhibited A beta(1-42)-induced tau hyperphosphorylation and rescued memory impairments in AD mouse models. Fc?RIIb phosphorylation at Tyr273 was found in AD brains, in neuronal cells exposed to A beta(1-42), and recruited SHIP2 to form a protein complex. Consequently, treatment with A beta(1-42) increased PtdIns(3,4)P-2 levels from PtdIns(3,4,5)P-3 to mediate tau hyperphosphorylation. Further, we found that targeting SHIP2 expression by lentiviral siRNA in 3xTg-AD mice or pharmacological inhibition of SHIP2 potently rescued tau hyperphosphorylation and memory impairments. Thus, we concluded that the Fc gamma RIIb-SHIP2 axis links A beta neurotoxicity to tau pathology by dysregulating PtdIns(3,4)P-2 metabolism, providing insight into therapeutic potential against AD. | - |
dc.language | English | - |
dc.publisher | ELIFE SCIENCES PUBLICATIONS LTD | - |
dc.title | Fc gamma RIIb-SHIP2 axis links A beta to tau pathology by disrupting phosphoinositide metabolism in Alzheimer's disease mode | - |
dc.type | Article | - |
dc.identifier.wosid | 000388499800001 | - |
dc.identifier.scopusid | 2-s2.0-84995414668 | - |
dc.type.rims | ART | - |
dc.citation.volume | 5 | - |
dc.citation.publicationname | ELIFE | - |
dc.identifier.doi | 10.7554/eLife.18691 | - |
dc.contributor.localauthor | Kam, Tae-In | - |
dc.contributor.localauthor | Park, Hyejin | - |
dc.contributor.nonIdAuthor | Gwon, Youngdae | - |
dc.contributor.nonIdAuthor | Song, Sungmin | - |
dc.contributor.nonIdAuthor | Kim, Seo-Hyun | - |
dc.contributor.nonIdAuthor | Moon, Seo Won | - |
dc.contributor.nonIdAuthor | Jo, Dong-Gyu | - |
dc.contributor.nonIdAuthor | Jung, Yong-Keun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | CELLULAR PRION PROTEIN | - |
dc.subject.keywordPlus | FC-GAMMA-RIIB | - |
dc.subject.keywordPlus | LONG-TERM POTENTIATION | - |
dc.subject.keywordPlus | AMYLOID-BETA | - |
dc.subject.keywordPlus | MEMORY IMPAIRMENT | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | INOSITOL 5&apos | - |
dc.subject.keywordPlus | -PHOSPHATASE-2 | - |
dc.subject.keywordPlus | SYNTHASE KINASE-3-BETA | - |
dc.subject.keywordPlus | SYNAPTIC PLASTICITY | - |
dc.subject.keywordPlus | NEGATIVE REGULATION | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.