Midori Suenaga, Hironobu Takahashi, Hiroshi Imagawa, Michiru Wagatsuma, Shinji Ouma, Yoshio Tsuboi, Akiko Furuta and Yoichi Matsunaga Pages 745 - 754 ( 10 )
The seeding of amyloid -β 40 ( Aβ40) oligomers from monomers is the initial step of A β aggregation, and many reports have suggested that cholesterol enhances this step. We studied the potential of secosteroid vitamin D derivatives for Aβ 40 aggregation in vitro. The quartz-crystal microbalance technique demonstrated that vitamin D3 does not show any effect on Aβ 40 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 Aβ 40 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 A β40 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. A β40 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 Aβ 40 aggregation and the docking simulation explains, why the same is not observed with vitamin D3.
Aggregation, Alzheimer's disease, amyloid-β , β -sheet formation, quartz-crystal microbalance technique, vitamin D derivatives.
Department of Medical Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.