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1、Targetingp-secretasewithRNAiinneuralstemcellsforAlzheimer'sdiseasetherapyZhonghuaLiuzShengliangLifZibinLiang,YanZhao,YulinZhangAYaqiYang,MinjuanWang,FengLiDepartmentofNeurobiologyandAnatomy,ZhongshanSchoolofMedicine,SunYat-senUniversity,Guangzhou510080,GuangdongProvinee
2、,ChinaAbstract:ThereareseveralmajorpathologicalchangesinAlzheimer'sdisease,includingapoptosisofcho-linergicneurons,overactivityoroverexpressionofp-siteamyloidprecursorproteincleavingenzyme1(BACE1)andinflammation.Inthisstudy,wesynthesizeda19-ntoligonucleotidetargetingBAC
3、E1,thekeyenzymeinamyloidbetaprotein(Ap)production,andintroduceditintothepSilenCirclevectortoconstructashorthairpin(shRNA)expressionplasmidagainsttheBACE1gene.WetransfectedthisvectorintoC17.2neuralstemcellsandprimaryneuralstemcells,resultingindownregulationoftheBACE1gene
4、,whichinturninducedaconsiderablereductioninreducingApproteinproduction.Weanticipatethatthistechniquecombiningcelltransplantationandgenether-apywillopenupnoveltherapeuticaverwesforAlzheimer'sdisease,particularlybecauseitcanbeusedtosimultaneouslytargetseveralpathogeneticc
5、hangesinthedisease.Keywords：neuralregeneration;neurodegenerativedisease;p-secretase;neuralstemcells;Alzheimer'sdisease;C17.2neuralstemcells;primaryneuralstemcells;shRNA;plasmid;geneticmodification;grants-supportedpaper;neuroregeneration;Acceptancedate:2013-06-01Citethis
6、article:ZhonghuaLiu,ShengliangLi,ZibinLiang,YanZhao,YulinZhang,YaqiYang,MinjuanWang,FengLi.Targetingp-secretasewithRNAiinneuralstemcellsforAlzheimer'sdiseasetherapy[J].NeuralRegenerationResearch,2013,8(33):3095-3106.
