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. 2022 Dec 29;13(51):11955-11960.
doi: 10.1021/acs.jpclett.2c03098. Epub 2022 Dec 19.

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

Yusuke Nakatani  1 , Naofumi Shimokawa  1 , Yasuomi Urano  2 , Noriko Noguchi  2 , Masahiro Takagi  1
Affiliations

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

Yusuke Nakatani et al. J Phys Chem Lett. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(a) Microscopic images of So/Ld phase separation at DOPC/DPPC = 50:50 (0% VE), (b) at DOPC/DPPC/Toc = 47.5:47.5:5 (5% Toc), and (c) at DOPC/DPPC/Toc3 = 47.5:47.5:5 (5% Toc3). (d) Microscopic image of homogeneous liposomes at DOPC/DPPC/Toc = 45:45:10 (10% Toc). Scale bars: 10 μm. (e) Fraction of phase-separated liposomes as a function of VE concentration. (f, g) Fraction of phase-separated liposomes containing Toc and Toc3, respectively, as a function of temperature.
Figure 2
Figure 2
DSC thermograph of membranes composed of (a) DPPC/Toc and (b) DPPC/Toc3. (c) Peak temperature changes of deconvoluted DSC thermographs as a function of VE concentration.
Figure 3
Figure 3
Microscopic images obtained by confocal laser scanning microscopy and fluorescence intensity profiles along the white lines in the merged images. Aβ protofibril adsorption on liposomes containing (a) 0% VE, (b) 10% Toc, and (c) 10% Toc3. Red and green fluorescence represent Rhod-DHPE and Aβ-488, respectively. Red and green lines in the fluorescence intensity profiles indicate the intensities of Rhod-DHPE and Aβ-488, respectively. Scale bars: 10 μm.
See this image and copyright information in PMC

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