As the most common cause of progressive intellectual failure in elderly humans, Alzheimer's disease (AD) is pathologically featured by amyloid plaques, synaptic loss, and neurofibrillary tangles. The amyloid plaques are mainly aggregates of amyloid β-peptide (Aβ), a primary factor contributing to the pathogenesis of AD. Elimination or reduction of the level of Aβ is considered an important strategy in AD treatment. The pharmacotherapeutic efficacy of selenium (Se), an essential biological trace element for mammalian species, has been confirmed in a number of experimental models of neurodegenerative diseases. Selenium-enriched yeast (Se-yeast) is commonly used as a nutritional supplement for Se. In this study, we investigated the effects and underlying mechanisms of Se-yeast on Aβ pathology in a 4-month-old triple transgenic mouse model of AD (3×Tg-AD mice). The administration of Se-yeast attenuated the deposition of Aβ in the brains of AD mice, which was concomitant with decreased levels of LC3II. The Se-yeast treatment decreased the level of amyloid-protein precursor (APP), downregulated the activity of AMP-activated protein kinase (AMPK) and upregulated the activity of AKT/mTOR/p70S6K. Furthermore, the levels of p62 also significantly decreased, and the cathepsin D levels increased, accompanied by increased turnover of Aβ and APP in Se-yeast-treated AD mice. In addition to decreasing the generation of Aβ, Se-yeast also inhibited the initiation of autophagy by modulating the AMPK/AKT/mTOR/p70S6K signaling pathway and enhanced autophagic clearance, thus reducing the burden of Aβ accumulation in the brains of AD mice. Our results further highlight the potential therapeutic effects of Se-yeast on AD.

中文翻译：

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在三重阿尔茨海默氏病转基因小鼠模型中，富硒酵母抑制β-淀粉样蛋白的产生并调节自噬

阿尔茨海默氏病（AD）是老年人进行性智力衰竭的最常见原因，其病理特征是淀粉样斑块，突触缺失和神经原纤维缠结。淀粉样斑块主要是淀粉样β-肽（Aβ）的聚集体，β-肽是导致AD发病的主要因素。消除或降低Aβ水平被认为是AD治疗中的重要策略。硒（Se）是哺乳动物物种必不可少的生物微量元素，在许多神经退行性疾病的实验模型中均已证实其药物治疗功效。富硒酵母（硒酵母）通常用作硒的营养补品。在这项研究中，我们在4个月大的AD三联转基因小鼠模型（3×Tg-AD小鼠）中研究了硒酵母对Aβ病理学的影响及其潜在机制。施用硒酵母可减轻AD小鼠大脑中Aβ的沉积，这与LC3II水平降低有关。硒酵母处理可降低淀粉样蛋白前体（APP）的水平，下调AMP激活的蛋白激酶（AMPK）的活性，并上调AKT / mTOR / p70S6K的活性。此外，在经酵母酵母处理的AD小鼠中，p62的水平也显着降低，组织蛋白酶D的水平升高，伴随着Aβ和APP的更新。除了减少Aβ的生成，Se-yeast还通过调节AMPK / AKT / mTOR / p70S6K信号通路和增强自噬清除来抑制自噬的启动，从而减轻了AD小鼠大脑中Aβ积累的负担。我们的结果进一步强调了硒酵母对AD的潜在治疗作用。