Anti-amyloidogenic effect of menaquinone-7 on beta-amyloid production and aggregation

Abstract

Purpose: To investigate the beneficial effects of menaquinone-7 (MK-7), an isoform of vitamin K-2, against beta-amyloid (A beta) production and aggregation in Alzheimer's disease using in vitro assays. Methods: The cytotoxicity of MK-7 was determined by MTT assay. The amount of A beta produced and secreted into the supernatant by APP-CHO cells treated with MK-7 was evaluated by ELISA. The expression of beta-secretases and ADAM10, a representative alpha-secretase, was determined using western blot analysis. The production of sAPP beta and sAPP alpha fragments generated by beta-secretases and alpha-secretase, respectively, were also determined by western blot analysis. The effect on A beta aggregation was assessed using Thioflavin T (Th T) assay. Results: MK-7 (up to 75 nM) significantly decreased A beta production in APP-CHO cells. This was accompanied by decreased expression of beta-secretase and lower production of sAPP beta (p < 0.05). However, expression of ADAM10 and production of sAPP alpha were not significantly affected. In contrast, MK-7 significantly decreased A beta aggregation in a dose-dependent manner (p < 0.05). Conclusion: MK-7 exerts anti-amyloidogenic effects via decreased production and lower aggregation of A beta into oligomers and fibrils. Therefore, dietary supplementation with MK-7 may be beneficial for the prevention of Alzheimer's disease.