维生素D2和D3对体外β淀粉样肽-40聚合物的不同作用

Title:Different Effect of Vitamin D₂ and Vitamin D₃ on Amyloid-β40 Aggregation In Vitro

Volume: 11 Issue: 8

Author(s): Midori Suenaga, Hironobu Takahashi, Hiroshi Imagawa, Michiru Wagatsuma, Shinji Ouma, Yoshio Tsuboi, Akiko Furuta and Yoichi Matsunaga

Affiliation:

关键词: 聚合物，阿尔茨海默病，β淀粉样蛋白，β-折叠形成，石英晶体微天平技术，维生素D衍生物

摘要: The seeding of amyloid-β 40 (Aβ40) oligomers from monomers is the initial step of Aβ aggregation, and many reports have suggested that cholesterol enhances this step. We studied the potential of secosteroid vitamin D derivatives for Aβ40 aggregation in vitro. The quartz-crystal microbalance technique demonstrated that vitamin D₃ does not show any effect on Aβ40 aggregation while vitamin D₂ promoted it and docking simulation but that vitamin D₂ has high potential in this regard. Thus, stacking of the Phe19 benzene ring in Aβ40 and the C22-C23 double bond in vitamin D₂ may alter the energy of these molecules. Electron microscopy revealed the potential of vitamin D₂ to increase Aβ40 aggregation. Thioflavin-T assays indicated that Vitamin D₂ induced increased fluorescence at 490 nm, as typically observed for amyloid fibrils but also for protofibrils; in both cases this reflects of the increase of β-sheet contents. Aβ40 aggregation was further confirmed in ELISA, SDS-PAGE and dot blot analysis which revealed changes in protease K resistance. These results suggest a possible mechanism, of how vitamin D₂ could increase Aβ40 aggregation and the docking simulation explains, why the same is not observed with vitamin D₃.

Cite this article as:

Midori Suenaga, Hironobu Takahashi, Hiroshi Imagawa, Michiru Wagatsuma, Shinji Ouma, Yoshio Tsuboi, Akiko Furuta and Matsunaga Yoichi, Different Effect of Vitamin D₂ and Vitamin D₃ on Amyloid-β40 Aggregation In Vitro, Current Alzheimer Research 2014; 11 (8) . https://dx.doi.org/10.2174/156720501108140910121139