Walnut-Derived Peptide PW5 Ameliorates Cognitive Impairments and Alters Gut Microbiota in APP/PS1 Transgenic Mice.
Walnut-Derived Peptide PW5 Ameliorates Cognitive Impairments and Alters Gut Microbiota in APP/PS1 Transgenic Mice.
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DOI：
10.1002/mnfr.201900326
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发表时间：
2019-09
影响因子：
5.2
通讯作者：
Min Wang;A. W. Kwame;Luohua Guo;Congcong Gong;Yuanhui Zhao;Maojin Yao;Jiaoyan Ren
中科院分区：
文献类型：
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作者：
Min Wang;A. W. Kwame;Luohua Guo;Congcong Gong;Yuanhui Zhao;Maojin Yao;Jiaoyan Ren
范围 减少 β-淀粉样蛋白 (Aβ) 积累对于寻找阿尔茨海默病 (AD) 认知障碍的治疗候选药物具有重要意义。本研究的目的是研究核桃蛋白活性成分在减少 Aβ 聚集和改善认知障碍方面的功效。方法与结果采用细胞内Aβ42聚集的细胞模型探讨核桃蛋白水解物(WPH)中的活性成分。合成了从 WPH 中鉴定出的具有出色抗 Aβ42 聚集活性的生物活性肽（Pro-Pro-Lys-Asn-Trp，PW5），用于体外和体内实验。使用经典的 APP/PS1 小鼠模型，我们验证了 PW5 通过减少 Aβ 斑块积累来发挥其认知改善作用。此外，代谢组学分析显示，与媒介物治疗的 APP/PS1 小鼠相比，PW5 干预后血清去甲肾上腺素 (NE) 和异戊酸水平显着升高，而血清乙酰胆碱 (ACe) 和戊酸水平降低。 16s rRNA 分析显示，PW5 喂养还通过增加厚壁菌门的相对丰度并减少变形菌和疣微菌，改善了 APP/PS1 转基因小鼠的肠道菌群失调。结论 这些有希望的结果支持肽 PW5 作为功能性食品中的活性成分或用于预防和/或治疗 AD 的潜在候选药物。本文受版权保护。版权所有。
SCOPE Decreasing β-amyloid (Aβ) accumulation is of significance in finding therapeutic candidates for cognitive impairments in Alzheimer's disease (AD). The aim of this study was to investigate the potency of the active components of walnut protein in decreasing Aβ aggregation and ameliorating cognitive impairments. METHODS AND RESULTS Cell model of intracellular Aβ42 aggregation was used to explore the active ingredients in walnut protein hydrolysate (WPH). A bioactive peptide (Pro-Pro-Lys-Asn-Trp, PW5) with great anti-Aβ42 aggregation activity identified from the WPH was synthesized for in vitro and in vivo experiments. Using classic APP/PS1 mouse model, we validated that PW5 exerted its effects on cognitive improvement through reducing Aβ plaques accumulation. Moreover, metabolomic analysis revealed that serum norepinephrine (NE) and isovalerate levels were significantly increased in response to PW5 intervention, with decreased serum levels of acetylcholine (AChe) and valerate, compared with the vehicle-treated APP/PS1 mice. PW5 feeding also improved gut dysbiosis in APP/PS1 transgenic mice by increasing the relative abundance of Firmicutes and decreasing Proteobacteria and Verrucomicrobia as displayed by 16s rRNA analyses. CONCLUSIONS These promising results support the utilization of peptide PW5 as an active ingredient in functional foods or potential drug candidate for the prevention and/or treatment of AD. This article is protected by copyright. All rights reserved.