School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan.
Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0394, Japan.
J Phys Chem Lett. 2022 Dec 29;13(51):11955-11960. doi: 10.1021/acs.jpclett.2c03098. Epub 2022 Dec 19.
Two forms of hydrophobic vitamin E (VE), α-tocopherol (Toc) and α-tocotrienol (Toc3), have been proposed to be effective against Alzheimer's disease (AD), the etiology of which is thought to involve endoplasmic reticulum (ER) stress. However, previous studies reported conflicting effects of Toc and Toc3 on the risk of AD. We prepared liposomes mimicking the phase separation of the ER membrane (solid-ordered/liquid-disordered phase separation) and studied how VE can influence the interaction between amyloid-β (Aβ) and the ER membrane. We found that Toc could inhibit the formation of the solid-ordered phase more significantly than Toc3. Furthermore, Aβ protofibril adsorption on ER stress-mimicking membranes was more strongly suppressed by Toc compared with Toc3. Therefore, we concluded that VE can relieve ER stress by destabilizing the solid-ordered phase of the ER membrane and subsequently reducing the amount of Aβ adsorbed on the membrane. Moreover, Toc exerted a stronger effect than Toc3.
两种形式的疏水性维生素 E（VE），α-生育酚（Toc）和α-生育三烯酚（Toc3），已被提议可有效对抗阿尔茨海默病（AD），其病因被认为涉及内质网（ER）应激。然而，先前的研究报告称 Toc 和 Toc3 对 AD 的风险影响相互矛盾。我们制备了模拟 ER 膜相分离的脂质体（固体有序/液体无序相分离），并研究了 VE 如何影响 Aβ 与 ER 膜的相互作用。我们发现 Toc 比 Toc3 更能显著抑制固体有序相的形成。此外，与 Toc3 相比，Toc 对 ER 应激模拟膜上 Aβ 原纤维的吸附抑制作用更强。因此，我们得出结论，VE 通过使 ER 膜的固体有序相失稳并随后减少吸附在膜上的 Aβ 量来缓解 ER 应激。此外，Toc 的作用比 Toc3 更强。
