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蛋白酶体功能与帕金森病相关性实验研究
作者:赵静        刘振国        陈生弟        陆国强        ZHAO Jing        LIU Zhen-guo        CHEN Sheng-di        LU Guo-qiang 
单位:上海第二医科大学附属瑞金医院神经内科 神经病学研究所 上海 200025 
关键词:Lactacystin      帕金森病      α-突触核蛋白      聚集 
分类号:R742.5
出版年,卷(期):页码:2005,12(6):0-0
摘要:
目的观察蛋白酶体抑制剂诱导大鼠黑质多巴胺能神经元α-突触核蛋白(α-synuclein,α-Syn)的表达及聚集,探讨蛋白酶体功能在帕金森病(PD)发病中的作用机制.方法采用立体定向将蛋白酶体抑制剂Lactacys-tin注射至大鼠黑质部位.以免疫荧光法观察黑质区多巴胺能神经元变性缺失,并应用免疫荧光双标法观察多巴胺能神经元内蛋白聚集的包涵体及其主要成分α-Syn的表达,然后通过原位杂交分析α-Syn mRNA表达及Western印迹法检测黑质α-Syn表达量改变.结果注射Lactacystin第7天大鼠开始出现自发性活动减少,阿扑吗啡尚可诱导出旋转行为;3周后患侧黑质部位酪氨酸羟化酶(TH)阳性细胞明显减少.TH与硫磺素、硫磺素与α-Syn复合染色呈阳性.α-Syn mRNA表达量升高,蛋白表达水平增加.结论Lactacystin诱导大鼠黑质细胞α-Syn表达升高并出现蛋白聚集可能是导致PD发病的机制之一.
基金项目:
上海市科委资助项目,上海市教委资助项目
作者简介:
参考文献:
Lorenzo A.Yankner BA Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red 1994(25) Hardy J.Rideout.Kristin E Proteasomal inhibition leads to formation of ubiquitin/α-Syn-immunoreactive inclusions in PC12 cells 2001 Breit S.Bouali-Benazzouz R.Benabid AL Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal activity of the pedunculopontine nucleus,which is reversed by the lesion of the subthalamic nucleus in the rat 2001 McNaught KS.Belezaire R.Isacson O Altered proteasomal function in Parkinson's disease 2003 Shastry BS Neurodegenerative disorders of protein aggregation 2003(01) Lee H J.Choi C.Lee SJ Membrane-bound α-Syn has a high aggregation propensity and the ability to seed the aggregation of the cytosolic form 2001 Biasin E.Fiorit L.Ceglia I Proteasome inhibition and aggregation in Parkinson's disease:a comparative study in untransfected and transfected cells 2004(03) Auluck PK.Chan E.Trojanowski JQ Chaperone suppression of alpha-synuclein toxicity in a Drosophila model of Parkinson's disease 2002 Bennett MC.Bishop JF.Leng Y Degradation of alpha-synuclein by proteasome 1999 Paxinou E.Chen Q.Weisse M Induction of alpha-synuclein aggregation by intracellular nitrative insult 2001
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