Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice.
Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice.
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DOI：
10.3233/jad-160685
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Tooyama I
中科院分区：
文献类型：
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作者：
Ibrahim NF;Yanagisawa D;Durani LW;Hamezah HS;Damanhuri HA;Wan Ngah WZ;Tsuji M;Kiuchi Y;Ono K;Tooyama I
阿尔茨海默病（AD）是痴呆症最常见的原因。AD的主要神经病理学特征是淀粉样蛋白-β（Aβ）积聚到细胞外斑块中，最终破坏神经元功能并导致神经变性。因此，一种可能的治疗策略是防止Aβ聚集。以前的研究表明，维生素E类似物可以减缓人类AD的进展。在本研究中，我们研究了富含生育三烯酚的组分（TRF），一种来自棕榈油的维生素E类似物的混合物，在体外和体内对淀粉样蛋白病理学的影响。TRF处理剂量依赖性地抑制体外Aβ纤维和Aβ寡聚体的形成。此外，与对照A β PPswe/PS1 dE 9小鼠相比，每日补充TRF 10个月可减轻脑中Aβ免疫反应性沉积和硫磺素-S阳性纤维状斑块，并最终改善新物体识别测试中的认知功能。目前的结果表明，TRF减少淀粉样病变和改善认知功能，并表明TRF是一个潜在的治疗剂AD。
Alzheimer’s disease (AD) is the most common cause of dementia. The cardinal neuropathological characteristic of AD is the accumulation of amyloid-β (Aβ) into extracellular plaques that ultimately disrupt neuronal function and lead to neurodegeneration. One possible therapeutic strategy therefore is to prevent Aβ aggregation. Previous studies have suggested that vitamin E analogs slow AD progression in humans. In the present study, we investigated the effects of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm oil, on amyloid pathology in vitro and in vivo. TRF treatment dose-dependently inhibited the formation of Aβ fibrils and Aβ oligomers in vitro. Moreover, daily TRF supplementation to AβPPswe/PS1dE9 double transgenic mice for 10 months attenuated Aβ immunoreactive depositions and thioflavin-S-positive fibrillar type plaques in the brain, and eventually improved cognitive function in the novel object recognition test compared with control AβPPswe/PS1dE9 mice. The present result indicates that TRF reduced amyloid pathology and improved cognitive functions, and suggests that TRF is a potential therapeutic agent for AD.