Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimers Disease 英文参考文献.docVIP

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Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimers Disease 英文参考文献.doc

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Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimers Disease 英文参考文献

Anti-AbDrugScreeningPlatformUsingHumaniPSCell- DerivedNeuronsfortheTreatmentofAlzheimer’s Disease NaokiYahata1,2,MasashiAsai2,3,4,ShihoKitaoka1,2,KazutoshiTakahashi1,IsaoAsaka1,2 ,Hiroyuki Hioki2,5,TakeshiKaneko5,KeiMaruyama3,TakaomiC.Saido4,TatsutoshiNakahata1,TakashiAsada6, ShinyaYamanaka1,7,NobuhisaIwata2,4,8*,HaruhisaInoue1,2,7 * 1CenterforiPSCellResearchandApplication,KyotoUniversity,Kyoto,Japan,2CoreResearchforEvolutionalScienceandTechnology,JapanScienceandTechnology Agency,Saitama,Japan,3DepartmentofPharmacology,FacultyofMedicine,SaitamaMedicalUniversity,Saitama,Japan,4LaboratoryforProteolyticNeuroscience,RIKEN Brain Science Institute, Saitama, Japan, 5Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 6Department of Neuropsychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan, 7Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Saitama,Japan,8GraduateSchoolofBiomedicalSciences,NagasakiUniversity,Nagasaki,Japan Abstract Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline during middletolate adultlife. The ADbrain is characterized by depositionof amyloid bpeptide (Ab),which is produced from amyloid precursor protein by b- and c-secretase (presenilin complex)-mediated sequential cleavage. Inducedpluripotentstem(iPS)cellspotentiallyprovideanopportunitytogenerateahumancell-basedmodelofADthat wouldbecrucialfordrugdiscoveryaswellasforinvestigatingmechanismsofthedisease. Methodology/Principal Findings: We differentiated human iPS (hiPS) cells into neuronal cells expressing the forebrain marker,Foxg1,andtheneocorticalmarkers,Cux1,Satb2,Ctip2,andTbr1.TheiPScell-derivedneuronalcellsalsoexpressed amyloidprecursorprotein,b-secretase,andc-secretasecomponents,andwerecapableofsecretingAbintotheconditioned media.Abproductionwasinhibitedbyb-secretaseinhibitor,c-secretaseinhibitor(GSI),andanNSAID;however,the