预览加载中，请您耐心等待几秒...

NADPH对KA介导的神经元兴奋性毒性的保护作用及其机制.docx

预览
1/3
2/3
3/3

在线预览结束，喜欢就下载吧，查找使用更方便

下载提示 文本预览

如果您无法下载资料，请参考说明：

1、部分资料下载需要金币，请确保您的账户上有足够的金币

2、已购买过的文档，再次下载不重复扣费

3、资料包下载后请先用软件解压，在使用对应软件打开

NADPH对KA介导的神经元兴奋性毒性的保护作用及其机制 Title:TheProtectiveRoleofNADPHAgainstKA-MediatedNeuronalExcitotoxicityandItsMechanisms Abstract: Neuronalexcitotoxicityisapathologicalprocesscharacterizedbyexcessiveneuronalactivityandsubsequentcelldeath.Kainicacid(KA),apotentagonistofglutamatereceptors,iswidelyusedtoinduceexcitotoxicityinexperimentalmodels.NADPH,acriticalcoenzymeinredoxreactions,hasbeenshowntopossessprotectiveeffectsagainstKA-mediatedneuronalexcitation.ThisreviewaimstoexplorethemechanismsbywhichNADPHexertsitsneuroprotectiveeffectsinthecontextofexcitotoxicityinducedbyKA. Introduction: Neurodegenerativediseases,stroke,andepilepsyareassociatedwiththeoccurrenceofexcitotoxicitymediatedbyexcessiveglutamatereleaseandsubsequentoveractivationofglutamatereceptors.Theseeventsleadtoanincreaseinintracellularcalciumlevels,mitochondrialdysfunction,oxidativestress,andultimatelycelldeath.Kainicacid(KA),apotentagonistofionotropicglutamatereceptors,caninduceexcitotoxicityandiswidelyusedasamodelcompoundinneurotoxicologicalresearch.However,recentstudieshaveshownthatNADPHpossessesprofoundneuroprotectiveeffectsagainstKA-inducedneuronalexcitotoxicity. MechanismsofNADPH-mediatedNeuroprotection: 1.RegulationofGlutamateExcitotoxicity: NADPHenhancesthefunctionofglutamatetransportersonastrocytes,promotingthereuptakeofextracellularglutamateandpreventingexcessiveglutamateaccumulation.Bymaintaininglowextracellularglutamatelevels,NADPHcanattenuateexcitotoxicity. 2.ModulationofCalciumHomeostasis: Excessivecalciuminfluxthroughglutamatereceptorstriggersacascadeofeventsleadingtocellulardamage.NADPHhasbeenreportedtoregulatecalciumchannels,reducingcalciuminfluxandpreventingexcitotoxicneuronaldamage. 3.PreservationofMitochondrialFunction: Mitochondrialdysfunctionisakeyeventinexcitotoxicity.NADPHactsasanessentialcofactorformitochondrialantioxidantenzymes,suchasglutathionereductaseandthioredoxinreductase,whichprotectagainstoxidativestress-inducedmitochondrialdamage. 4.AntioxidantDefense: NADPHplaysacriticalrole