β-淀粉样蛋白基元序列寡聚化及纤维化的功能研究  

Dissection of the Interplay among the Motifs within Amyloid Beta Peptide in Processes of Oligomerization and Fibrillation

作　　者：石镜明[1] 李岩松[1] 陈文玲[1] 贺学[1] 吴涛[1] 武美娜[1] 

机构地区：[1]西藏民族大学基础医学院,高原环境与疾病相关基因研究实验室,陕西咸阳712082

出　　处：《重庆师范大学学报（自然科学版）》2017年第1期95-99,共5页Journal of Chongqing Normal University:Natural Science

基　　金：西藏自治区自然科学基金(No.12KJZRZMY02,2015zr-13-12)

摘　　要：【目的】β-淀粉样蛋白形成的寡聚体是引起阿尔茨海默症(Alzheimer disease,AD)发病的主要原因之一,研究β-淀粉样蛋白各段序列在寡聚和纤维化过程中的作用,以便更好地阐明该蛋白的寡聚机制和毒性作用。【方法】以C-端及N-端删节的6种β-淀粉样肽段作为研究对象,通过硫磺素T荧光检测、Tris-Tricine电泳、透射电镜等方法定性定量分析这些肽段的寡聚化和纤维化能力。【结果】1)氨基酸37~42具有增强Aβ寡聚化和纤维化的功能;2)氨基酸18~36对于寡聚和纤维化很重要,但不能缺少N-端的参与;3)Aβ1-17参与β-淀粉样蛋白长纤维的形成。【结论】β-淀粉样蛋白各段氨基酸序列对该蛋白寡聚和纤维化所贡献的不同作用,这对于β-淀粉样蛋白毒性机制的研究起到一定的帮助作用。[Purposes]β-amyloid oligomers are one of the main causes of Alzheimer＇s disease.Explicating the structure and function of each segment motif in the sequence ofβ-amyloid peptide which forms soluble oligomer and fiber was the target in this paper.[Methods]Six C-and N-terminal end of truncatedβ-amyloid peptides were used to analysis their oligomerization and fibrillation capability.Use Thioflavin- T（ThT）fluorescence detection,Tris-Tricine electrophoresis and transmission electron microscope（TEM）methods to clarify the role of the amino acid motifs in the process of oligomerization and fibrillation.[Findings]The results show：1）Amino acids 37~42can enhance Aβoligomerization and fibrillation function;2）Amino acids 18~36is important for oligomerization and fibrillation,but cannot lack participation of N-terminal;3）Aβ1-17 is necessary for the formation of long Aβfibre.[Conclusions]Amino acid sequence ofβ-amyloid protein can contribute different roles in the process of oligomerization and fibrillation.These research results may provide a strong reference to clarify the role of Aβtoxicity in AD.

关 键 词：Β-淀粉样蛋白 删节肽段 寡聚 纤维 

分 类 号：Q518.4[生物学—生物化学]