敲除α-突触核蛋白保护多巴胺能神经元
甲基苯丙胺诱导的帕金森病模型中多巴胺能神经元死亡的主要因素是α-突触核蛋白过表达。
中国南方医科大学王慧君博士所在团队发现，立体定位注射α-syn-shRNA慢病毒抑制右侧纹状体α-synmRNA和蛋白的表达后，帕金森病模型大鼠抑郁表现减弱，且纹状体中多巴胺水平和酪氨酸羟化酶及超氧化物歧化酶活性显着增加，而活性氧生成量、一氧化氮合酶活性、一氧化氮含量和丙二醛含量下降，同时纹状体中凋亡细胞的数量明显降低。
作者认为，α-突触核蛋白具有通过抑制氧化应激和改善多巴胺能系统功能扭转甲基苯丙胺诱导的神经毒性的能力。
相关文献发表于《中国神经再生研究（英文版）》杂志2014年5月第9期。
TUNEL染色结果显示，以立体定向注射α-syn-shRNA慢病毒敲除右侧纹状体中α-syn后，腹腔注射甲基苯丙胺建立帕金森病模型大鼠纹状体中凋亡细胞的数量显着降低
Article:"Protectiveeffectofalpha-synucleinknockdownonmethamphetamine-inducedneurotoxicityindopamin ergicneurons,"byYunchunTai1,LingChen1,EnpingHuang1,ChaoLiu1,2,XingyiYang1,PingmingQiu1,HuijunWang1(1DepartmentofF orensicMedicine,SchoolofBasicMedicalSciences,SouthernMedicalUniversity,Guangzhou,GuangdongProvince,China;2GuangzhouFore
nsicScienceInstitute,Guangzhou,GuangdongProvince,China)
TaiYC,ChenL,HuangEP,LiuC,YangXY,QiuPM,WangHJ.Protectiveeffectofalpha-synucleinknockdownonmethamphetamine-inducedneurotoxicityindopaminergicn eurons.NeuralRegenRes.2014;9(9):951-958.
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NeuralRegenRes
Protectiveeffectofα-synucleinknockdownondopaminergicneurons
Theover-expressionofα-synucleinisamajorfactorinthedeathofdopaminergicneuronsinamethamphetamine-indu cedmodelofParkinson’sdisease(PD).Dr.HuijunWang,SchoolofBasicMedicalSciences,SouthernMedicalUniver sity,Chinaandhisteaminjectedα-synuclein-shRNAlentivirusstereotaxicallyintotherightstriatumofexperimentalr atstoinhibitα-synucleinmRNAandproteinexpression.Resultsshowedthatafterα-synucleinknockdown,thedepres sionmanifestationsofPDratswerereduced,striataldopamineandtyrosinehydroxylaselevelsaswellassuperoxidedi smutaseactivityweresignificantlyincreased,butthelevelsofreactiveoxygenspecies,malondialdehyde,nitricoxide synthaseandnitrogenmonoxideweredecreased,andsimultaneously,thenumberofapoptoticcellsinthestriatumwas
significantlydecreased.Theauthorsconsideredα-synucleinhasthecapacitytoreversemethamphetamine-induceda poptosisofdopaminergicneuronsintheratstriatumbyinhibitingoxidativestressandimprovingdopaminergicsyste mfunction.RelatedresultswerepublishedinNeuralRegenerationResearch(Vol.9,No.9,2014).
Afterα-synu cleinknockdownbystereotaxicinjectionofα-synucleinintotherightstriatum,thenumberofapoptoticcellsinthestriatum ofratmodelsofmtamfetamine-inducedAlzheimer’sdisease wassignificantlyreduced,asshownbyTUNELstaining. Article:"Protectiveeffectofalpha-synucleinknockdownonmethamphetamine-inducedneurotoxicityindopamin ergicneurons,"byYunchunTai1,LingChen1,EnpingHuang1,ChaoLiu1,2,XingyiYang1,PingmingQiu1,HuijunWang1(1DepartmentofF orensicMedicine,SchoolofBasicMedicalSciences,SouthernMedicalUniversity,Guangzhou,GuangdongProvince,China;2GuangzhouFore nsicScienceInstitute,Guangzhou,GuangdongProvince,China)
TaiYC,ChenL,HuangEP,LiuC,YangXY,QiuPM,WangHJ.Protectiveeffectofalpha-synucleinknockdownonmethamphetamine-inducedneurotoxicityindopaminergicn eurons.NeuralRegenRes.2014;9(9):951-958.。