https://scholars.lib.ntu.edu.tw/handle/123456789/470001
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Kapoor A. | en_US |
dc.contributor.author | Wang B.-J. | en_US |
dc.contributor.author | WEN-MING HSU | en_US |
dc.contributor.author | Chang M.-Y. | en_US |
dc.contributor.author | Liang S.-M. | en_US |
dc.contributor.author | Liao Y.-F. | en_US |
dc.creator | Liao Y.-F.;Liang S.-M.;Chang M.-Y.;WEN-MING HSU;Wang B.-J.;Kapoor A. | - |
dc.date.accessioned | 2020-03-05T03:20:17Z | - |
dc.date.available | 2020-03-05T03:20:17Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 1948-7193 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84880381926&doi=10.1021%2fcn400039s&partnerID=40&md5=6d038c6db25ace732743c86855d3057a | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/470001 | - |
dc.description.abstract | Retinoic acid (RA)-elicited signaling has been shown to play critical roles in development, organogenesis, and the immune response. RA regulates expression of Alzheimer's disease (AD)-related genes and attenuates amyloid pathology in a transgenic mouse model. In this study, we investigated whether RA can suppress the production of amyloid-β (Aβ) through direct inhibition of γ-secretase activity. We report that RA treatment of cells results in significant inhibition of γ-secretase-mediated processing of the amyloid precursor protein C-terminal fragment APP-C99, compared with DMSO-treated controls. RA-elicited signaling was found to significantly increase accumulation of APP-C99 and decrease production of secreted Aβ40. In addition, RA-induced inhibition of γ-secretase activity was found to be mediated through significant activation of extracellular signal-regulated kinases (ERK1/2). Treatment of cells with the specific ERK inhibitor PD98059 completely abolished RA-mediated inhibition of γ-secretase. Consistent with these findings, RA was observed to inhibit secretase-mediated proteolysis of full-length APP. Finally, we have established that RA inhibits γ-secretase through nuclear retinoic acid receptor-α (RARα) and retinoid X receptor-α (RXRα). Our findings provide a new mechanistic explanation for the neuroprotective role of RA in AD pathology and add to the previous data showing the importance of RA signaling as a target for AD therapy. ? 2013 American Chemical Society. | - |
dc.relation.ispartof | ACS Chemical Neuroscience | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | 2 (2 amino 3 methoxyphenyl)chromone; amyloid beta protein; amyloid precursor protein; dimethyl sulfoxide; gamma secretase; mitogen activated protein kinase 1; retinoic acid; retinoic acid receptor alpha; retinoid X receptor alpha; article; controlled study; embryo; enzyme activation; enzyme activity; enzyme inhibition; enzyme repression; human; human cell; priority journal; protein cleavage; protein degradation; signal transduction; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Cells, Cultured; Humans; MAP Kinase Signaling System; Retinoid X Receptor alpha; Signal Transduction; Tretinoin | - |
dc.title | Retinoic acid-elicited RARα/RXRα signaling attenuates aβ production by directly inhibiting γ-secretase-mediated cleavage of amyloid precursor protein | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1021/cn400039s | - |
dc.identifier.pmid | 23530929 | - |
dc.identifier.scopus | 2-s2.0-84880381926 | - |
dc.relation.pages | 1093-1100 | - |
dc.relation.journalvolume | 4 | - |
dc.relation.journalissue | 7 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.orcid | 0000-0002-5145-9538 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學系 |
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