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J Nutr Health Aging. 2015 Jun;19(6):646-56. doi: 10.1007/s12603-015-0506-z.
The E vitamins are a class of lipophilic compounds including tocopherols, which have high antioxidative properties. Because of the elevated lipid peroxidation and increased reactive oxidative species in Alzheimer's disease (AD) many attempts have been made to slow down the progression of AD by utilizing the antioxidative action of vitamin E. Beside the mixed results of these studies nothing is known about the impact of vitamin E on the mechanisms leading to amyloid-β production and degradation being responsible for the plaque formation, one of the characteristic pathological hallmarks in AD. Here we systematically investigate the influence of different tocopherols on Aβ production and degradation in neuronal cell lines.
Beside amyloid-β level the mechanisms leading to Aβ production and degradation are examined.
Surprisingly, all tocopherols have shown to increase Aβ level by enhancing the Aβ production and decreasing the Aβ degradation. Aβ production is enhanced by an elevated activity of the involved enzymes, the β- and γ-secretase. These secretases are not directly affected, but tocopherols increase their protein level and expression. We could identify significant differences between the single tocopherols; whereas α-tocopherol had only minor effects on Aβ production, δ-tocopherol showed the highest potency to increase Aβ generation. Beside Aβ production, Aβ clearance was decreased by affecting IDE, one of the major Aβ degrading enzymes.
Our results suggest that beside the beneficial antioxidative effects of vitamin E, tocopherol has in respect to AD also a potency to increase the amyloid-β level, which differ for the analysed tocopherols. We therefore recommend that further studies are needed to clarify the potential role of these various vitamin E species in respect to AD and to identify the form which comprises an antioxidative property without having an amyloidogenic potential.
生育酚是一类亲脂性化合物，包括具有高抗氧化性能的生育酚。由于阿尔茨海默病（AD）中的脂质过氧化和活性氧物质增加，许多人试图利用维生素 E 的抗氧化作用来减缓 AD 的进展。除了这些研究的混合结果外，对于维生素 E 对导致淀粉样蛋白-β产生和降解的机制的影响一无所知，这些机制负责斑块形成，是 AD 的特征性病理标志之一。在这里，我们系统地研究了不同生育酚对神经元细胞系中 Aβ 产生和降解的影响。
除了淀粉样蛋白-β水平外，还检查了导致 Aβ 产生和降解的机制。
令人惊讶的是，所有生育酚都通过增强 Aβ 的产生和降低 Aβ 的降解来增加 Aβ 水平。Aβ 的产生是通过参与的酶，即β-和γ-分泌酶的活性升高而增强的。这些分泌酶没有直接受到影响，但生育酚增加了它们的蛋白水平和表达。我们可以识别出单个生育酚之间的显著差异；虽然α-生育酚对 Aβ 的产生只有较小的影响，但δ-生育酚显示出增加 Aβ 生成的最高效力。除了 Aβ 的产生，Aβ 的清除也通过影响 IDE 而降低，IDE 是主要的 Aβ 降解酶之一。
我们的结果表明，除了维生素 E 的有益抗氧化作用外，生育酚在 AD 方面也具有增加淀粉样蛋白-β水平的作用，这与分析的生育酚不同。因此，我们建议需要进一步的研究来阐明这些不同的维生素 E 物质在 AD 方面的潜在作用，并确定具有抗氧化特性而没有淀粉样蛋白形成潜力的形式。
