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000136732 0247_ $$2doi$$a10.1523/JNEUROSCI.2681-12.2012
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000136732 0247_ $$2pmc$$apmc:PMC6621731
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000136732 0247_ $$2ISSN$$a1529-2401
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000136732 041__ $$aEnglish
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000136732 1001_ $$0P:(DE-HGF)0$$aPage, Richard M$$b0
000136732 245__ $$aLoss of PAFAH1B2 reduces amyloid-β generation by promoting the degradation of amyloid precursor protein C-terminal fragments.
000136732 260__ $$aWashington, DC$$bSoc.57413$$c2012
000136732 264_1 $$2Crossref$$3online$$bSociety for Neuroscience$$c2012-12-12
000136732 264_1 $$2Crossref$$3print$$bSociety for Neuroscience$$c2012-12-12
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000136732 520__ $$aAmyloid-β peptide (Aβ) is believed to play a central role in the pathogenesis of Alzheimer's disease. In view of the side effects associated with inhibiting the secretases that produce Aβ, new molecular targets are required to provide alternative therapeutic options. We used RNA interference (RNAi) to systematically screen the Drosophila genome to identify genes that modulate Aβ production upon knockdown. RNAi of 41 genes in Drosophila cells significantly lowered Aβ without affecting general secretion or viability. After the γ-secretase complex components, the most potent effect was observed for platelet activating factor acetylhydrolase α (Paf-AHα), and, in mammalian cells, the effect was replicated for its ortholog PAFAH1B2. Knockdown of PAFAH1B2 strongly reduced Aβ secretion from human cells, and this effect was confirmed in primary cells derived from PAFAH1B2 knock-out mice. Reduced Aβ production was not attributable to altered β-amyloid precursor protein (APP) ectodomain shedding but was a result of an enhanced degradation of APP C-terminal fragments (CTFs) in the absence of PAFAH1B2 but not its close homolog PAFAH1B3. Enhanced degradation of APP CTFs was selective because no such effects were obtained for Notch or E-/N-cadherin. Thus, we have identified an important protein that can selectively modify Aβ generation via a novel mechanism, namely enhanced degradation of its immediate precursor. In view of the absence of a neurological phenotype in PAFAH1B2 knock-out mice, targeted downregulation of PAFAH1B2 may be a promising new strategy for lowering Aβ.
000136732 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000136732 542__ $$2Crossref$$i2013-06-12$$uhttps://creativecommons.org/licenses/by-nc-sa/4.0/
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000136732 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000136732 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000136732 650_7 $$2NLM Chemicals$$aMicrotubule-Associated Proteins
000136732 650_7 $$2NLM Chemicals$$aPeptide Fragments
000136732 650_7 $$0EC 3.1.1.47$$2NLM Chemicals$$a1-Alkyl-2-acetylglycerophosphocholine Esterase
000136732 650_7 $$0EC 3.1.1.47$$2NLM Chemicals$$aPAFAH1B1 protein, human
000136732 650_2 $$2MeSH$$a1-Alkyl-2-acetylglycerophosphocholine Esterase: genetics
000136732 650_2 $$2MeSH$$a1-Alkyl-2-acetylglycerophosphocholine Esterase: metabolism
000136732 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000136732 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: metabolism
000136732 650_2 $$2MeSH$$aAnimals
000136732 650_2 $$2MeSH$$aDrosophila
000136732 650_2 $$2MeSH$$aGene Knockdown Techniques
000136732 650_2 $$2MeSH$$aHEK293 Cells
000136732 650_2 $$2MeSH$$aHumans
000136732 650_2 $$2MeSH$$aMice
000136732 650_2 $$2MeSH$$aMice, Knockout
000136732 650_2 $$2MeSH$$aMicrotubule-Associated Proteins: genetics
000136732 650_2 $$2MeSH$$aMicrotubule-Associated Proteins: metabolism
000136732 650_2 $$2MeSH$$aPeptide Fragments: metabolism
000136732 650_2 $$2MeSH$$aRNA Interference
000136732 650_2 $$2MeSH$$aTransfection
000136732 7001_ $$0P:(DE-HGF)0$$aMünch, Anna$$b1
000136732 7001_ $$0P:(DE-HGF)0$$aHorn, Thomas$$b2
000136732 7001_ $$0P:(DE-2719)2810327$$aKuhn, Peer-Hendrik$$b3
000136732 7001_ $$0P:(DE-2719)2340744$$aColombo, Alessio$$b4
000136732 7001_ $$aReiner, Orly$$b5
000136732 7001_ $$aBoutros, Michael$$b6
000136732 7001_ $$0P:(DE-2719)2000023$$aSteiner, Harald$$b7
000136732 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b8
000136732 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b9$$eLast author
000136732 77318 $$2Crossref$$3journal-article$$a10.1523/jneurosci.2681-12.2012$$bSociety for Neuroscience$$d2012-12-12$$n50$$p18204-18214$$tThe Journal of Neuroscience$$v32$$x0270-6474$$y2012
000136732 773__ $$0PERI:(DE-600)1475274-8$$a10.1523/JNEUROSCI.2681-12.2012$$gVol. 32, no. 50, p. 18204 - 18214$$n50$$p18204-18214$$q32:50<18204 - 18214$$tThe journal of neuroscience$$v32$$x0270-6474$$y2012
000136732 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621731
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000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/oxfordjournals.jbchem.a003145
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1091/mbc.E09-12-1064
000136732 999C5 $$1Blank$$2Crossref$$9-- missing cx lookup --$$a10.1016/S0021-9258(19)70115-X$$p175 -$$tJ Biol Chem$$v256$$y1981
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrg2364
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1091266
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/gb-2006-7-7-r66
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.nbd.2008.10.014
000136732 999C5 $$1Chen$$2Crossref$$9-- missing cx lookup --$$a10.1016/S0021-9258(19)39742-X$$p3116 -$$tJ Biol Chem$$v265$$y1990
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrd2896
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/360672a0
000136732 999C5 $$1Colombo$$2Crossref$$oColombo 2012$$y2012
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.132277899
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ncb960
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.95.23.13703
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.0283-04.2004
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/sj.emboj.7600061
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrm2101
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/357500a0
000136732 999C5 $$1Haass$$2Crossref$$9-- missing cx lookup --$$a10.1016/S0021-9258(18)53650-4$$p3021 -$$tJ Biol Chem$$v268$$y1993
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nm1295-1291
000136732 999C5 $$1Hattori$$2Crossref$$9-- missing cx lookup --$$a10.1016/S0021-9258(17)46693-2$$p18748 -$$tJ Biol Chem$$v268$$y1993
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature09325
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/gb-2010-11-6-r61
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1385/MN:30:2:185
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M211836200
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/emboj.2010.167
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1471-4159.2010.07081.x
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0014-5793(99)00730-9
000136732 999C5 $$1Livnat$$2Crossref$$oLivnat 2010$$y2010
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/1756-6606-3-11
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.0605461103
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/emboj/cdf541
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M708754200
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M110.103283
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.1026-07.2007
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.273.5279.1227
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.287.5461.2204
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/30756
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1749-6632.1996.tb34401.x
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/(SICI)1097-0134(20000401)39:1<1::AID-PROT1>3.0.CO;2-N
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M110.102277
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.1230693100
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/35041097
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.R800010200
000136732 999C5 $$1Tarricone$$2Crossref$$oTarricone 2004$$y2004
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1160649
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.R800019200
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.1236145100
000136732 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0000252