Ibrahim Nor Faeizah, Hamezah Hamizah Shahirah, Yanagisawa Daijiro, Tsuji Mayumi, Kiuchi Yuji, Ono Kenjiro, Tooyama Ikuo
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia.
Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600, UKM Bangi, Selangor, Malaysia.
Biochem Biophys Rep. 2021 Sep 10;28:101131. doi: 10.1016/j.bbrep.2021.101131. eCollection 2021 Dec.
One of the neuropathological hallmarks of Alzheimer's disease (AD)-causing neurodegeneration and consequent memory deterioration, and eventually, cognitive decline-is amyloid-β (Aβ) aggregation forming amyloid plaques. Our previous study showed the potential of a tocotrienol-rich fraction-a mixture of naturally occurring of vitamin E analogs-to inhibit Aβ aggregation and restore cognitive function in an AD mouse model. The current study examined the effect of three vitamin E analogs-α-tocopherol (α-TOC), α-tocotrienol (α-T3), and γ-tocotrienol (γ-T3)-on Aβ aggregation, disaggregation, and oligomerization in vitro. Thioflavin T (ThT) assay showed α-T3 reduced Aβ aggregation at 10 μM concentration. Furthermore, both α-T3 and γ-T3 demonstrated Aβ disaggregation, as shown by the reduction of ThT fluorescence. However, α-TOC showed no significant effect. We confirmed the results for ThT assays with scanning electron microscopy imaging. Further investigation in photo-induced cross-linking of unmodified protein assay indicated a reduction in Aβ oligomerization by γ-T3. The present study thus revealed the individual effect of each tocotrienol analog in reducing Aβ aggregation and oligomerization as well as disaggregating preformed fibrils.
阿尔茨海默病（AD）导致神经退行性变以及随之而来的记忆衰退，最终导致认知能力下降，其神经病理学标志之一是淀粉样β蛋白（Aβ）聚集形成淀粉样斑块。我们之前的研究表明，富含生育三烯酚的组分（一种天然存在的维生素E类似物混合物）在AD小鼠模型中具有抑制Aβ聚集和恢复认知功能的潜力。当前研究检测了三种维生素E类似物——α-生育酚（α-TOC）、α-生育三烯酚（α-T3）和γ-生育三烯酚（γ-T3）——对体外Aβ聚集、解聚和寡聚化的影响。硫黄素T（ThT）检测表明，α-T3在10μM浓度下可减少Aβ聚集。此外，α-T3和γ-T3均表现出Aβ解聚，这可通过ThT荧光降低得以证明。然而，α-TOC未显示出显著效果。我们通过扫描电子显微镜成像证实了ThT检测的结果。对未修饰蛋白质的光诱导交联检测的进一步研究表明，γ-T3可减少Aβ寡聚化。因此，本研究揭示了每种生育三烯酚类似物在减少Aβ聚集和寡聚化以及解聚预先形成的纤维方面的个体作用。
