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一项基因表达数据的荟萃分析突出了阿尔茨海默病患者大脑中海马区的突触功能障碍。

A meta-analysis of gene expression data highlights synaptic dysfunction in the hippocampus of brains with Alzheimer's disease.

机构信息

Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.

Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

出版信息

Sci Rep. 2020 May 20;10(1):8384. doi: 10.1038/s41598-020-64452-z.

Abstract

Since the world population is ageing, dementia is going to be a growing concern. Alzheimer's disease is the most common form of dementia. The pathogenesis of Alzheimer's disease is extensively studied, yet unknown remains. Therefore, we aimed to extract new knowledge from existing data. We analysed about 2700 upregulated genes and 2200 downregulated genes from three studies on the CA1 of the hippocampus of brains with Alzheimer's disease. We found that only the calcium signalling pathway enriched by 48 downregulated genes was consistent between all three studies. We predicted miR-129 to target nine out of 48 genes. Then, we validated miR-129 to regulate six out of nine genes in HEK cells. We noticed that four out of six genes play a role in synaptic plasticity. Finally, we confirmed the upregulation of miR-129 in the hippocampus of brains of rats with scopolamine-induced amnesia as a model of Alzheimer's disease. We suggest that future research should investigate the possible role of miR-129 in synaptic plasticity and Alzheimer's disease. This paper presents a novel framework to gain insight into potential biomarkers and targets for diagnosis and treatment of diseases.

摘要

随着世界人口老龄化,痴呆症将成为一个日益关注的问题。阿尔茨海默病是最常见的痴呆症形式。阿尔茨海默病的发病机制已经得到广泛研究,但仍有许多未知之处。因此,我们旨在从现有数据中提取新知识。我们分析了来自三个关于阿尔茨海默病患者海马体 CA1 的研究中的约 2700 个上调基因和 2200 个下调基因。我们发现,只有在所有三个研究中都富集的钙信号通路是一致的。我们预测 miR-129 可能靶向 48 个下调基因中的 9 个。然后,我们在 HEK 细胞中验证了 miR-129 对其中 6 个基因的调节作用。我们注意到,这 6 个基因中的 4 个在突触可塑性中发挥作用。最后,我们证实了 miR-129 在东莨菪碱诱导的记忆障碍大鼠海马体中的上调,东莨菪碱诱导的记忆障碍是阿尔茨海默病的模型。我们建议未来的研究应该调查 miR-129 在突触可塑性和阿尔茨海默病中的可能作用。本文提出了一种新的框架,以深入了解潜在的生物标志物和治疗靶点,用于疾病的诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8557/7239885/190b81903702/41598_2020_64452_Fig1_HTML.jpg

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