肌萎缩性脊髓侧索硬化症相关蛋白SOD1的氨基酸突变对其聚集的影响  

Effects of Amyotrophic Lateral Sclerosis Associated SOD1 Amino Acid Mutations on Aggregation

作　　者：刘佳骏[1,2] 孙茂民[2,3] 刘枫[2] 王晓春[2,3] 

机构地区：[1]同济大学生物医学工程研究所,上海200092 [2]苏州大学系统生物学研究中心,江苏苏州215006 [3]苏州大学医学部人体解剖与组织胚胎学系,江苏苏州215123

出　　处：《苏州大学学报（医学版）》2009年第3期411-414,共4页Suzhou University Journal of Medical Science

基　　金：国家自然科学基金资助项目(20872107)

摘　　要：目的探讨肌萎缩性脊髓侧索硬化症(ALS)发病过程中超氧化物歧化酶1(SOD1)氨基酸突变对其聚集的影响。方法收集全部已知SOD1氨基酸错义突变106个,运用AGGRESCAN、PASTA、TANGO3种生物信息学方法和工具,预测错义突变对蛋白质聚集倾向的作用。结果3种生物信息学工具预测结果基本一致,共有39个对蛋白质聚集有促进作用的突变,占所有突变的37%。结论氨基酸突变导致蛋白质聚集并非是导致ALS发病的唯一途径,ALS发病机制是一个多因素的复杂过程。Objective To investigate the effects of SOD1 mutation -aggregation in amyotrophic lateral sclerosis （ALS） and to improve the understanding of the molecular mechanism of the disease. Methods To predict the effects of aggregation propensity with amino acid mutations, all known 106 missense mutations in SOD1 were collected and analyzed with 3 kinds of bioinformatics tools and methods, AGGRESCAN, PASTA and TANGO. Results The predicting outcome of 3 tools are similar and 39 mutations, accounting 37%, were considered to enhance the aggregation propensity. Conclusion The pathogenesis of ALS is supposed to be a multi-factors process. Protein aggregation caused by amino acid mutations is not the only important factor that amino acid mutations cause ALS disease.

关 键 词：肌萎缩性脊髓侧索硬化症 超氧化物歧化酶1 氨基酸突变 蛋白质聚集 生物信息学分析 

分 类 号：R744.8[医药卫生—神经病学与精神病学]