Suppression of Amyloid-β Adsorption on Endoplasmic Reticulum Stress-Mimicking Membranes by α-Tocopherol and α-Tocotrienol

Two forms of hydrophobic vitamin E (VE), alpha-tocopherol (Toc) and alpha-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-beta (A beta) and the ER membrane. We found that Toc could inhibit the formation of the solid-ordered phase more significantly than Toc3. Furthermore, A beta 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 A beta adsorbed on the membrane. Moreover, Toc exerted a stronger effect than Toc3.

Automated summary

The hydrophobic vitamin E can relieve endoplasmic reticulum stress by destabilizing the solid-ordered phase of the ER membrane, leading to a reduction in the adsorption of amyloid-beta. Among them, α-tocopherol has a stronger effect than α-tocotrienol.