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β淀粉样蛋白 1-42 改变皮质神经元中 miRNAs 的表达。

Amyloid Beta 1-42 Alters the Expression of miRNAs in Cortical Neurons.

机构信息

Brain and Neurodegenerative Disorders Research Laboratory, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey.

Department of Medical Biology, Faculty of Medicine, Altinbas University, Istanbul, Turkey.

出版信息

J Mol Neurosci. 2019 Feb;67(2):181-192. doi: 10.1007/s12031-018-1223-y. Epub 2018 Dec 4.

DOI:10.1007/s12031-018-1223-y
PMID:30515701
Abstract

Recently, Aβ1-42 was demonstrated to have the potential to translocate into the nucleus and to be involved in the transcriptional regulation of certain neurodegeneration-related genes. This data raises the question of whether Aβ-induced neurodegeneration might include the expression of miRNAs. Thus, our aim in this study was to investigate the effects of Aβ1-42 on certain miRNAs which are related with vitamin D metabolism, neuronal differentiation, development, and memory. This question was investigated in primary cortical neurons that were treated with 10 μM Aβ and/or 10 M 1,25-dihydroxyvitamin D3 at different time points by expression analysis of let-7a-5p, miR-26b-5p, miR-27b-3p, miR-31a-5p, miR-125b-5p, and miR-192-5p with qRT-PCR. Our data indicate that amyloid pathology has effects on the expression of miRNAs. Furthermore, some of these miRNAs simultaneously regulate the proteins or the enzymes involved in neuronal metabolism. The experimental setup that we used and the data we acquired supply valuable information about the miRNAs that play a part in the Aβ pathology and suggested Aβ as a counterpart of vitamin D at the crossroads of neuronal differentiation, development, and memory.

摘要

最近,研究表明 Aβ1-42 具有向细胞核易位的潜力,并参与某些与神经退行性变相关基因的转录调控。这一数据引发了一个问题,即 Aβ 诱导的神经退行性变是否可能包括 miRNA 的表达。因此,我们在这项研究中旨在研究 Aβ1-42 对某些与维生素 D 代谢、神经元分化、发育和记忆相关的 miRNA 的影响。我们通过表达分析来研究这个问题,在不同时间点用 10 μM Aβ 和/或 10 μM 1,25-二羟维生素 D3 处理原代皮质神经元,用 qRT-PCR 检测 let-7a-5p、miR-26b-5p、miR-27b-3p、miR-31a-5p、miR-125b-5p 和 miR-192-5p 的表达。我们的数据表明淀粉样蛋白病理学对 miRNA 的表达有影响。此外,这些 miRNA 中的一些同时调节神经元代谢中涉及的蛋白质或酶。我们使用的实验设置和获得的数据提供了关于在 Aβ 病理学中起作用的 miRNA 的有价值的信息,并提出 Aβ 作为神经元分化、发育和记忆交汇点的维生素 D 的对应物。

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