Nucleosome assembly protein 1-like 5 alleviates Alzheimer's disease-like pathological characteristics in a cell model.

Nucleosome assembly protein 1-like 5 alleviates Alzheimer's disease-like pathological characteristics in a cell model.
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DOI:
10.3389/fnmol.2022.1034766
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发表时间:
2022
影响因子:
4.8
通讯作者:
Sun, Fengxian
Sun, Fengxian
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Bingyan;Liu, Weiying;Sun, Fengxian

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阿尔茨海默病(Alzheimer's disease,AD)是神经退行性疾病中最常见的痴呆之一。核小体组装蛋白1样5(NAP 1 L5)属于NAP 1 L蛋白家族,其作为组蛋白伴侣。然而,NAP 1 L5在AD中的作用和机制尚不清楚。生物信息学分析、RT-qPCR和Western blotting结果表明,NAP 1 L5在AD患者脑组织和AD小鼠细胞模型中表达下调。NAP 1 L5过表达减轻(淀粉样蛋白-β前体蛋白)APP代谢和Tau磷酸化。我们进一步证明NAP 1 L5通过GSK 3B/Wnt/β-Catenin信号通路调节AD样病理特征。此外,我们还发现N2 a-APP 695 sw细胞中由NAP 1 L5调控的Wnt/β-Catenin信号通路是由AQP 1介导的。总之,这些结果表明,NAP 1 L5过表达具有神经保护作用,并可能作为诊断和治疗AD的潜在生物标志物和靶点。
Alzheimer’s disease (AD) remains one of the most common dementias of neurodegenerative disease-related diseases. Nucleosome assembly protein 1-like 5 (NAP1L5) belongs to the NAP1L protein family, which acts as a histone chaperone. However, the function and mechanism of NAP1L5 in AD are still unclear. Bioinformatics analysis, RT-qPCR, and Western blotting results showed that NAP1L5 was downregulated in the brain tissues of AD patients and a mouse cell model of AD. NAP1L5 overexpression alleviated (Amyloid-β precursor protein) APP metabolism and Tau phosphorylation. We further demonstrated that NAP1L5 regulated the AD-like pathological characteristics through the GSK3B/Wnt/β-Catenin signaling pathway. Moreover, we showed that the Wnt/β-Catenin signaling pathway, regulated by NAP1L5, was mediated by AQP1-mediated mechanism in N2a-APP695sw cell. In sum, these results suggested that NAP1L5 overexpression has neuroprotective effects and might act as potential biomarker and target for the diagnosis and treatment of AD.
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