https://scholars.lib.ntu.edu.tw/handle/123456789/469972
DC 欄位 | 值 | 語言 |
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dc.contributor.author | Wang, B.-J., Her, G.M., Hu, M.-K., Chen, Y.-W., Tung, Y.-T., Wu, P.-Y., Hsu, W.-M., Lee, H., Jin, L.-W., Hwang, S.-P.L., Chen, R.P.-Y., Huang, C.-J., Liao, Y.-F. | en_US |
dc.contributor.author | Her G.M. | en_US |
dc.contributor.author | Hu M.-K. | en_US |
dc.contributor.author | Chen Y.-W. | en_US |
dc.contributor.author | Tung Y.-T. | en_US |
dc.contributor.author | Wu P.-Y. | en_US |
dc.contributor.author | WEN-MING HSU | en_US |
dc.contributor.author | Lee H. | en_US |
dc.contributor.author | Jin L.-W. | en_US |
dc.contributor.author | Hwang S.-P.L. | en_US |
dc.contributor.author | Chen R.P.-Y. | en_US |
dc.contributor.author | Huang C.-J. | en_US |
dc.contributor.author | HSINYU LEE | en_US |
dc.creator | Wang B.-J.;Her G.M.;Hu M.-K.;Chen Y.-W.;Tung Y.-T.;Wu P.-Y.;Wen-Ming Hsu;Lee H.;Jin L.-W.;Hwang S.-P.L.;Chen R.P.-Y.;Huang C.-J.;Liao Y.-F. | - |
dc.date.accessioned | 2020-03-05T03:20:08Z | - |
dc.date.available | 2020-03-05T03:20:08Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85035053134&doi=10.1073%2fpnas.1618804114&partnerID=40&md5=28e86a2524929b443a907348d8fcd281 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/469972 | - |
dc.description.abstract | Proteolytic processing of amyloid precursor protein (APP) C-terminal fragments (CTFs) by γ-secretase underlies the pathogenesis of Alzheimer’s disease (AD). An RNA interference screen using APP-CTF [99-residue CTF (C99)]- and Notch-specific γ-secretase interaction assays identified a unique ErbB2-centered signaling network that was predicted to preferentially govern the proteostasis of APP-C99. Consistently, significantly elevated levels of ErbB2 were confirmed in the hippocampus of human AD brains. We then found that ErbB2 effectively suppressed autophagic flux by physically dissociating Beclin-1 from the Vps34–Vps15 complex independent of its kinase activity. Down-regulation of ErbB2 by CL-387,785 decreased the levels of C99 and secreted amyloid-β in cellular, zebrafish, and mouse models of AD, through the activation of autophagy. Oral administration of an ErbB2-targeted CL-387,785 for 3 wk significantly improves the cognitive functions of APP/presenilin-1 (PS1) transgenic mice. This work unveils a noncanonical function of ErbB2 in modulating autophagy and establishes ErbB2 as a therapeutic target for AD. ? 2017, National Academy of Sciences. All rights reserved. | - |
dc.publisher | National Academy of Sciences | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | amyloid beta protein; amyloid precursor protein; beclin 1; epidermal growth factor receptor 2; gamma secretase; mitogen activated protein kinase; Notch receptor; phosphatidylinositol 3 kinase; presenilin 1; protein serine threonine kinase VPS15; sequestosome 1; stress activated protein kinase; amyloid beta protein; amyloid precursor protein; beclin 1; epidermal growth factor receptor 2; ERBB2 protein, human; presenilin 1; secretase; Alzheimer disease; animal cell; animal experiment; animal model; Article; autophagy; carboxy terminal sequence; cognition; comparative study; controlled study; embryo; enzyme activity; female; hippocampus; human; human tissue; memory; mouse; neuropathology; newborn; nonhuman; Notch signaling; priority journal; protein expression; protein homeostasis; protein protein interaction; protein secretion; protein targeting; receptor down regulation; regulatory mechanism; spatial learning; zebra fish; Alzheimer disease; animal; brain; genetics; growth, development and aging; male; metabolism; pathology; protein homeostasis; transgenic mouse; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Autophagy; Beclin-1; Brain; Female; Humans; Male; Mice; Mice, Transgenic; Presenilin-1; Proteostasis; Receptor, ErbB-2; Zebrafish | - |
dc.title | ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer’s disease | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1073/pnas.1618804114 | - |
dc.identifier.pmid | 28351972 | - |
dc.identifier.scopus | 2-s2.0-85035053134 | - |
dc.relation.pages | E3129-E3138 | - |
dc.relation.journalvolume | 114 | - |
dc.relation.journalissue | 15 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Biomedical Electronics and Bioinformatics | - |
crisitem.author.dept | Life Science | - |
crisitem.author.dept | Center for Biotechnology | - |
crisitem.author.dept | Electrical Engineering | - |
crisitem.author.orcid | 0000-0002-5145-9538 | - |
crisitem.author.orcid | 0000-0002-1477-0183 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Electrical Engineering and Computer Science | - |
crisitem.author.parentorg | College of Life Science | - |
crisitem.author.parentorg | Others: University-Level Research Centers | - |
crisitem.author.parentorg | College of Electrical Engineering and Computer Science | - |
顯示於: | 醫學系 |
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