应用DIGE测定帕金森病脑脊液中蛋白变化  

Analysis of cerebrospinal fluid protein expression in Parkinson＇s disease by two-dimensional difference gel electrophoresis

作　　者：王尔松[1] 高翔[1] 周嘉伟[3] 胡杰[1] 夏鹰[2] 郭继光[3] 呼建文[4] 江澄川[1] 

机构地区：[1]复旦大学附属华山医院神经外科.上海市神经外科临床医学中心,上海200040 [2]复旦大学附属上海市第五人民医院神经外科,上海200240 [3]中国科学院上海生命科学院生化和细胞所,上海200031 [4]中国科学院上海生命科学院蛋白质组研究分析中心,上海200031

出　　处：《中华神经医学杂志》2008年第6期585-588,共4页Chinese Journal of Neuromedicine

基　　金：上海市科委科研计划（04dz14005）

摘　　要：目的测定帕金森病（PD）脑脊液中蛋白的变化，为进一步探索PD的生物标记物提供线索。方法采用荧光差异凝胶电泳技术分离并筛选PD和正常对照者脑脊液中差异表达蛋白质．用基质辅助激光解吸电离飞行时间质谱（MALDI—TOFMS）或串联质谱技术进行鉴定并分析。结果共发现20个明显的差异蛋自点，其中11个点在PD中上调，9个点下调，共鉴定出8个蛋白质，其中有3个未知蛋白，均表现为下调。蛋白MYPTl出现明显下调，载脂蛋白原、脂蛋白发生明显上调，载脂蛋白A—I的一个异构体发生上调，一个异构体发生下调。结论MYPT1与突触功能有关，载脂蛋白原、脂蛋白、载脂蛋白A—I与胆固醇代谢有关，这些蛋白与PD发生有一定关联，有可能成为PD的生物标记物。Objective To identify differentially expressed proteins in cerebrospinal fluid （CSF） of Parkinson＇s disease （PD）, so as to provide clues for investigating PD biomarkers. Methods Two-dimensional difference gel electrophoresis （2D DIGE） technique, in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF MS）, was used to determine the differentially expressed CSF proteins in PD patients in comparison with control subjects. Results The levels of 20 protein spots were significantly altered in PD CSF. Of them, 11 spots were up-regulated and 9 spots were down-regulated. Of the 8 proteins identified in the profile of differentially expressed protein spots between patients and controls, an isoform of apolipoprotein A-I, myosin phosphatase target subunit 1 （MYPT1）, and 3 unknown proteins were down-regulated, whereas an apolipoprotein A-I isoform, proapolipoprotein, and lipoprotein were up-regulated. Conclusions MYPT1 is related with synapse function and proapolipoprotein, lipoprotein and apo A-I are associated with cholesterol metabolism. These proteins may have links with the pathogenesis of PD and may be identified as CSF biomarks in PD.

关 键 词：帕金森病 脑脊液 生物标记物 蛋白质组学 

分 类 号：R742.5[医药卫生—神经病学与精神病学]