原子力显微镜在α-Synuclein积聚和解聚研究中的应用  

Applications of atomic force microscopy in studying the α-Synuclein's aggregation and disaggregation

作　　者：唐琳[1] 李洪涛[2] 杜海宁[2] 吉丽娜[1] 张峰[1] 李民乾[1] 胡红雨[2] 胡钧[1] 

机构地区：[1]中国科学院上海原子核研究所纳米生物医药实验室,上海201800 [2]中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海200031

出　　处：《电子显微学报》2003年第2期116-119,共4页Journal of Chinese Electron Microscopy Society

基　　金：国家自然科学基金资助项目 (No .NSFC39990 60 0 ;No.19890 385 );中国科学院特别支持项目 (No .STZ97 2 0 2;STZ 0 0 0 7);国家杰出青年基金 (No .1972 5 415 );上海市优秀学科带头人资助计划 (No .0 0XD14 4 40 2 9)资助项目

摘　　要：研究α Synuclein蛋白纤维的积聚和解聚过程对于帕金森症等神经退化性疾病的预防和治疗有着重要意义。本文利用原子力显微镜对α Synuclein的积聚过程的不同阶段进行了研究 ,并在此基础上对已经积聚形成的α Synuclein纤维在溶液中的解聚过程进行了原位观察。实验结果表明 :α Synuclein积聚过程包括单体→寡聚体→短纤维→长纤维这几个阶段 ;而α Synuclein纤维在浓度降低的情况下 ,会发生解聚 ,解聚是从纤维的中间发生断裂开始 ,经过一段时间后 。Studying the aggregation and disaggregation processes of α-synuclein fibrils is very meaningful for the therapy of these neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. In this paper, the α-synuclein at different stages of its aggregation process was observed by atomic force microscopy. And the disaggregation process of α-synuclein fibrils was monitored by in situ atomic force microscopy in solution. It was found that the process of α-synuclein fibrillization included several stages: (a) oligomerization from monomers. (b) formation of short fibrils. (c) maturation of fibrils and that α-synuclein fibrils could disaggregate step by step in solution when diluted to some extent. The disaggregation usually started at the middle of the fibrils, and as time went by, the long fibrils could disaggregate into some short fragments and particles with different sizes. Relevant mechanism has been discussed.

关 键 词：原子力显微镜 α—Synuclein 神经退化性疾病 帕金森氏综合症 积聚 解聚 

分 类 号：R318.6[医药卫生—生物医学工程]