Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 현동훈 | * |
dc.date.accessioned | 2016-08-28T10:08:28Z | - |
dc.date.available | 2016-08-28T10:08:28Z | - |
dc.date.issued | 2012 | * |
dc.identifier.issn | 1474-9718 | * |
dc.identifier.other | OAK-9004 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/222834 | - |
dc.description.abstract | The cause of elevated level of amyloid β-peptide (Aβ42) in common late-onset sporadic [Alzheimer's disease (AD)] has not been established. Here, we show that the membrane lipid peroxidation product 4-hydroxynonenal (HNE) is associated with amyloid and neurodegenerative pathologies in AD and that it enhances γ-secretase activity and Aβ42 production in neurons. The γ-secretase substrate receptor, nicastrin, was found to be modified by HNE in cultured neurons and in brain specimens from patients with AD, in which HNE-nicastrin levels were found to be correlated with increased γ-secretase activity and Aβ plaque burden. Furthermore, HNE modification of nicastrin enhanced its binding to the γ-secretase substrate, amyloid precursor protein (APP) C99. In addition, the stimulation of γ-secretase activity and Aβ42 production by HNE were blocked by an HNE-scavenging histidine analog in a 3xTgAD mouse model of AD. These findings suggest a specific molecular mechanism by which oxidative stress increases Aβ42 production in AD and identify HNE as a novel therapeutic target upstream of the γ-secretase cleavage of APP. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. | * |
dc.language | English | * |
dc.title | Oxidative lipid modification of nicastrin enhances amyloidogenic γ-secretase activity in Alzheimer's disease | * |
dc.type | Article | * |
dc.relation.issue | 4 | * |
dc.relation.volume | 11 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 559 | * |
dc.relation.lastpage | 568 | * |
dc.relation.journaltitle | Aging Cell | * |
dc.identifier.doi | 10.1111/j.1474-9726.2012.00817.x | * |
dc.identifier.wosid | WOS:000306400600001 | * |
dc.identifier.scopusid | 2-s2.0-84864012821 | * |
dc.author.google | Gwon A.-R. | * |
dc.author.google | Park J.-S. | * |
dc.author.google | Arumugam T.V. | * |
dc.author.google | Kwon Y.-K. | * |
dc.author.google | Chan S.L. | * |
dc.author.google | Kim S.-H. | * |
dc.author.google | Baik S.-H. | * |
dc.author.google | Yang S. | * |
dc.author.google | Yun Y.-K. | * |
dc.author.google | Choi Y. | * |
dc.author.google | Kim S. | * |
dc.author.google | Tang S.-C. | * |
dc.author.google | Hyun D.-H. | * |
dc.author.google | Cheng A. | * |
dc.author.google | Dann C.E. | * |
dc.author.google | Bernier M. | * |
dc.author.google | Lee J. | * |
dc.author.google | Markesbery W.R. | * |
dc.author.google | Mattson M.P. | * |
dc.author.google | Jo D.-G. | * |
dc.contributor.scopusid | 현동훈(7005049041) | * |
dc.date.modifydate | 20240123112641 | * |