Cited 15 times in
Selective inhibition of PCAF suppresses microglial-mediated β-amyloid neurotoxicity
DC Field | Value | Language |
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dc.contributor.author | 박수연 | - |
dc.contributor.author | 윤호근 | - |
dc.date.accessioned | 2014-12-18T08:55:03Z | - |
dc.date.available | 2014-12-18T08:55:03Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 1107-3756 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/87190 | - |
dc.description.abstract | Recent studies have emphasized the functional role of the P300/CBP-associated factor (PCAF) enzyme in resistance to β-amyloid (Aβ)-mediated neurotoxicity; however, the underlying mechanisms through which PCAF regulates inflammation and neurotoxicity have not yet been elucidated. In this study, we used computer-based molecular docking simulations to perform structure-based artificial screening for PCAF-specific inhibitors. Our results revealed that one of the compounds from the screened library, compound C-11, selectively inhibited PCAF, but not p300 or GCN5, with a half-maximal inhibitory concentration (IC50) of approximately 0.25 µM. Furthermore, C-11 had no effects on the activities of other epigenetic enzymes. Western blot analysis using an antibody against acetyl-nuclear factor-κB (NF-κB) demonstrated that PCAF mediated the Aβ-induced activation of NF-κB by acetylation at Lys-122. We also found that the knockdown of PCAF completely inhibited Aβ-induced cytokine production in BV-2 cells in a similar manner to C-11 treatment. Finally, PCAF inhibition suppressed both Aβ-induced cytokine production and Aβ-mediated neuronal cell death. Therefore, our results suggest that in neuronal cells, PCAF is a promising therapeutic target for alleviating the inflammatory progression of Alzheimer's disease. | - |
dc.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Selective inhibition of PCAF suppresses microglial-mediated β-amyloid neurotoxicity | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biochemistry & Molecular Biology (생화학,분자생물학) | - |
dc.contributor.googleauthor | Soo-Yeon Park | - |
dc.contributor.googleauthor | Yoo-Hyun Lee | - |
dc.contributor.googleauthor | Ah-Reum Seong | - |
dc.contributor.googleauthor | Jeongmin Lee | - |
dc.contributor.googleauthor | Woojin Jun | - |
dc.contributor.googleauthor | Ho-Geun Yoon | - |
dc.identifier.doi | 10.3892/ijmm.2013.1407 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02625 | - |
dc.contributor.localId | A01534 | - |
dc.relation.journalcode | J01132 | - |
dc.identifier.eissn | 1791-244X | - |
dc.identifier.url | http://www.spandidos-publications.com/ijmm/32/2/469 | - |
dc.contributor.alternativeName | Park, Soo Yeon | - |
dc.contributor.alternativeName | Yoon, Ho Geun | - |
dc.contributor.affiliatedAuthor | Yoon, Ho Geun | - |
dc.contributor.affiliatedAuthor | Park, Soo Yeon | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 32 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 469 | - |
dc.citation.endPage | 475 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, Vol.32(2) : 469-475, 2013 | - |
dc.identifier.rimsid | 32547 | - |
dc.type.rims | ART | - |
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