促进Aβ42形成不溶性聚集物的一种真菌化合物  

Promoting action of demethoxyviridin on Aβ42 oligomers to form insoluble macromolecule aggregates

作　　者：邹永东[1,2] 梁泽秋 董瑶[1,3] 陈国栋[4] 刘国宝[1,2] 郑易之[1,2] 

机构地区：[1]深圳大学生命与海洋科学学院,广东深圳518060 [2]深圳市微生物基因工程重点实验室,广东深圳518060 [3]深圳市海洋生物资源与生态环境重点实验室,广东深圳518060 [4]暨南大学药学院,中药及天然药物研究所,广东广州510632

出　　处：《深圳大学学报（理工版）》2016年第1期25-32,共8页Journal of Shenzhen University(Science and Engineering)

基　　金：国家自然科学基金资助项目(81202441)~~

摘　　要：β-类淀粉蛋白42(amyloid-β42,Aβ42)聚集形成的可溶性寡聚体具有神经细胞毒性,是引起阿尔茨海默症的主要原因之一.通过浊度法、聚丙烯酰胺凝胶电泳(sodium dodecyl sulfate-polyacrylamide gelelectrophoresis,SDS-PAGE)和原子力显微镜(atomic force microscopy,AFM)技术,分析在真菌化合物demethoxyviridin存在情况下,Aβ42聚集过程中荧光强度、浊度、寡聚体和聚集物的比例及颗粒表观形态等动态变化之间的对应关系.结果表明,化合物demethoxyviridin可明显促进Aβ42小分子寡聚体形成高分子量寡聚体后,形成不溶性大分子聚集物沉淀,减少可溶性Aβ42寡聚体比例.探讨了硫磺素T荧光法、浊度法、SDS-PAGE法和AFM法在研究Aβ42聚集及活性化合物影响Aβ42聚集中的互补性,认为综合应用4种方法有助于揭示活性化合物影响Aβ42寡聚体沉淀形成的分子机理.）Amyloid beta（ Aβ） is crucially involved in Alzheimer＇s disease,and soluble Aβ 42 oligomers are the main neurotoxic species. In this paper,the experimental methods,including standard thioflavin T（ Th T） fluorescence assay,turbimetric method,sodium dodecyl sulfate-polyacrylamide gelelectrophoresis（ SDS-PAGE） and atomic force microscopy（ AFM）,are applied to investigate the relationship among the thioflavin T fluorescence,the turbidi-ty,the proportion and the surface shape of Aβ42 oligomers and aggregates during the Aβ42 aggregation procedure.The results show that the fungal compound demethoxyviridin could clearly promote soluble small molecular Aβ42 oligomers to form insoluble macromolecular aggregate precipitates via high molecular weight oligomers. In addition,the complementarities of the Th T fluorescence assay,turbimetric method,SDS-PAGE and AFM on Aβ 42 aggregation procedure are discussed. The comprehensive application of these methods is helpful to reveal the molecular mechanism of the effect of the active compounds on the formation of Aβ 42 oligomers and their precipitation.

关 键 词：微生物药物学 阿尔茨海默症 β-类淀粉蛋白 Aβ42寡聚体 Aβ42聚集 Aβ42大分子聚集沉淀 真菌化合物 

分 类 号：R93[医药卫生—生药学]