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首页> 外文期刊>The Journal of Nutritional Biochemistry >Resveratrol confers neuroprotection against high-fat diet in a mouse model of Alzheimer's disease via modulation of proteolytic mechanisms
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Resveratrol confers neuroprotection against high-fat diet in a mouse model of Alzheimer's disease via modulation of proteolytic mechanisms

机译：白藜芦醇通过调制蛋白水解机制来赋予阿尔茨海默病小鼠模型中的高脂饮食神经保护饮食

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摘要

Cumulative evidence indicates that excessive consumption of calories from saturated fat contributes to the development of Alzheimer's disease (AD). Here, we assess the triggering and progression of AD pathology induced by a high-fat diet (HFD), and the effects of resveratrol, a polyphenol found in common dietary sources with pleiotropic neuroprotective activities. Over 16 weeks, male wild type (WT) and AD transgenic 5XFAD mice were fed a control diet, HFD (60% kcal from fat), or HFD supplemented with 0.1% resveratrol. Resveratrol protected against HFD-induced memory loss in WT mice and prevented memory loss in 5XFAD mice. Resveratrol also reduced the amyloid burden aggravated by HFD in 5XFAD, and protected against HFD-induced tau pathology in both WT and 5XFAD strains. At the mechanistic level, resveratrol inhibited the HFD-increased amyloidogenic processing of the amyloid precursor protein in both strains; it also restored abnormal high levels in the proteolytic activity of the ubiquitin-proteasome system induced by HFD, suggesting the presence of a compensatory mechanism to counteract the accumulation of aberrant proteins. Thus, our data suggest that resveratrol can correct the harmful effects of HFD in the brain and may be a potential therapeutic agent against obesity-related disorders and AD pathology. (c) 2020 Elsevier Inc. All rights reserved.
机译：累积证据表明，过量摄入饱和脂肪中的卡路里会导致阿尔茨海默病（AD）的发展。在这里，我们评估了高脂饮食（HFD）诱发的AD病理学的触发和进展，以及白藜芦醇的作用，白藜芦醇是一种在常见饮食来源中发现的具有多效性神经保护活性的多酚。在16周内，雄性野生型（WT）和AD转基因5XFAD小鼠被喂食对照饮食、HFD（60%来自脂肪的kcal）或添加0.1%白藜芦醇的HFD。白藜芦醇对WT小鼠HFD诱导的记忆丧失有保护作用，对5XFAD小鼠的记忆丧失有预防作用。白藜芦醇还降低了5XFAD中因HFD而加重的淀粉样蛋白负荷，并对WT和5XFAD菌株中HFD诱导的tau病变具有保护作用。在机制层面上，白藜芦醇抑制了两种菌株中HFD增加的淀粉样前体蛋白的淀粉样变性过程；它还恢复了HFD诱导的泛素-蛋白酶体系统蛋白水解活性的异常高水平，表明存在一种代偿机制来抵消异常蛋白质的积累。因此，我们的数据表明，白藜芦醇可以纠正HFD对大脑的有害影响，并且可能是一种潜在的治疗剂，用于治疗肥胖相关疾病和AD病理学。（c） 2020爱思唯尔公司版权所有。

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