DC Field | Value | Language |
---|---|---|
dc.contributor.author | Gwon, Youngdae | ko |
dc.contributor.author | Kam, Tae-In | ko |
dc.contributor.author | Kim, Seo-Hyun | ko |
dc.contributor.author | Song, Sungmin | ko |
dc.contributor.author | Park, Hyejin | ko |
dc.contributor.author | Lim, Bitna | ko |
dc.contributor.author | Lee, Haneul | ko |
dc.contributor.author | Lee, Weontae | ko |
dc.contributor.author | Jo, Dong-Gyu | ko |
dc.contributor.author | Jung, Yong-Keun | ko |
dc.date.accessioned | 2023-03-10T09:00:53Z | - |
dc.date.available | 2023-03-10T09:00:53Z | - |
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 | 2018-10 | - |
dc.identifier.citation | JOURNAL OF NEUROSCIENCE, v.38, no.42, pp.9001 - 9018 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | http://hdl.handle.net/10203/305551 | - |
dc.description.abstract | Emerging evidences suggest that intraneuronal A beta correlates with the onset of Alzheimer's disease (AD) and highly contributes to neurodegeneration. However, critical mediator responsible for A beta uptake in AD pathology needs to be clarified. Here, we report that Fc gamma RIIb2, a variant of Fc gamma-receptor IIb (Fc gamma RIIb), functions in neuronal uptake of pathogenic A beta. Cellular accumulation of oligomeric A beta(1-42), not monomeric A beta(1-42) or oligomeric A beta(1-40), was blocked by Fcgr2b knock-out in neurons and partially in astrocytes. A beta(1-42) internalization was Fc gamma RIIb2 di-leucine motif-dependent and attenuated by TOM1, a Fc gamma RIIb2-binding protein that repressed the receptor recycling. TOM1 expression was downregulated in the hippocampus of male 3xTg-AD mice and AD patients, and regulated by miR-126-3p in neuronal cells after exposure to A beta(1-42). In addition, memory impairments in male 3xTg-AD mice were rescued by the lentiviral administration of TOM1 gene. Augmented A beta uptake into lysosome caused its accumulation in cytoplasm and mitochondria. Moreover, neuronal accumulation of A beta in both sexes of 3xTg-AD mice and memory deficits in male 3xTg-AD mice were ameliorated by forebrain-specific expression of A beta-uptake-defective Fcgr2b mutant. Our findings suggest that Fc gamma RIIb2 is essential for neuropathic uptake of A beta in AD. | - |
dc.language | English | - |
dc.publisher | SOC NEUROSCIENCE | - |
dc.title | TOM1 Regulates Neuronal Accumulation of Amyloid-beta Oligomers by Fc gamma RIIb2 Variant in Alzheimer's Disease | - |
dc.type | Article | - |
dc.identifier.wosid | 000447587500008 | - |
dc.identifier.scopusid | 2-s2.0-85055152300 | - |
dc.type.rims | ART | - |
dc.citation.volume | 38 | - |
dc.citation.issue | 42 | - |
dc.citation.beginningpage | 9001 | - |
dc.citation.endingpage | 9018 | - |
dc.citation.publicationname | JOURNAL OF NEUROSCIENCE | - |
dc.identifier.doi | 10.1523/JNEUROSCI.1996-17.2018 | - |
dc.contributor.localauthor | Kam, Tae-In | - |
dc.contributor.localauthor | Park, Hyejin | - |
dc.contributor.nonIdAuthor | Gwon, Youngdae | - |
dc.contributor.nonIdAuthor | Kim, Seo-Hyun | - |
dc.contributor.nonIdAuthor | Song, Sungmin | - |
dc.contributor.nonIdAuthor | Lim, Bitna | - |
dc.contributor.nonIdAuthor | Lee, Haneul | - |
dc.contributor.nonIdAuthor | Lee, Weontae | - |
dc.contributor.nonIdAuthor | Jo, Dong-Gyu | - |
dc.contributor.nonIdAuthor | Jung, Yong-Keun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Alzheimer&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | Amyloid beta (A beta) | - |
dc.subject.keywordAuthor | Intraneuronal A beta | - |
dc.subject.keywordAuthor | Fc gamma | - |
dc.subject.keywordAuthor | receptor IIb | - |
dc.subject.keywordAuthor | TOM1 | - |
dc.subject.keywordAuthor | miR-126 | - |
dc.subject.keywordPlus | INTRANEURONAL A-BETA | - |
dc.subject.keywordPlus | FC-GAMMA-RIIB | - |
dc.subject.keywordPlus | CELL-SURFACE | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | ENDOCYTOSIS | - |
dc.subject.keywordPlus | CLEARANCE | - |
dc.subject.keywordPlus | PATHOLOGY | - |
dc.subject.keywordPlus | TAU | - |
dc.subject.keywordPlus | APP | - |
dc.subject.keywordPlus | NEURODEGENERATION | - |
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