過飽和の解消による蛋白質の異常凝集体の形成に関する研究

今年，我将我对蛋白质聚集的研究从球状蛋白扩展到了一种内在无序的蛋白质，淀粉样蛋白β 1-40。淀粉样蛋白β 1-40的错误折叠和聚集与阿尔茨海默病的发病有关。虽然对淀粉样蛋白β 1-40聚集的研究已经做了很多，但其具体机制还不完全清楚，本论文以乙醇为溶剂，应用超声技术，从宏观角度研究了淀粉样蛋白β 1-40聚集的微观机制和途径。结果表明，淀粉样蛋白β 1-40的微观聚集途径依赖于醇的浓度和类型。此外，添加盐诱导淀粉样蛋白β 1-40从非途径寡聚体转化为途径内原纤维。在此基础上，构建了淀粉样蛋白β 1-40在醇中聚集的相图，表明溶解度和过饱和度的概念也为淀粉样蛋白β 1-40的聚集提供了一个宏观的理解，这些结果为淀粉样蛋白β 1 - 40的聚集过程提供了进一步的认识。其有利于开发控制淀粉样蛋白β 1-40聚集的小分子。

I extended my study on protein aggregation from globular proteins to an intrinsically disordered protein, amyloid beta 1-40, this year. Misfolding and aggregation of amyloid beta 1-40 has been related to the onset of Alzheimer’s disease. Although much has been done to explore amyloid beta 1-40 aggregation, its detail mechanism is only partially understood.I investigated the microscopic mechanism and pathway of amyloid beta 1-40 aggregation with macroscopic viewpoints using alcohols with the application of ultrasonication. The results suggested that the microscopic aggregation pathways of amyloid beta 1-40 depended on concentration and type of alcohols. Moreover, the addition of salts induced conversion of amyloid beta 1-40 from off-pathway oligomers into in-pathways protofibrils. Based on experimental results, I constructed phase diagrams of amyloid beta 1-40 aggregation in alcohols, which indicated that the concept of solubility and supersaturation also provided a macroscopic understanding of amyloid beta 1-40 aggregation.In conclusion, these results gave a further insight into the aggregation process of amyloid beta 1-40, which is beneficial for developing small molecules to control amyloid beta 1-40 aggregation.