MicroRNAs (miRNAs) are small noncoding RNAs, which regulate numerous cell functions by targeting mRNA for cleavage or translational repression, and have been found to play an important role in Alzheimer’s disease (AD). Our study aimed to identify differentially expressed miRNAs in AD brain as a reference of potential therapeutic miRNAs or biomarkers for this disease. We used amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice and age-matched wild-type (WT) littermates to determine the expression of miRNAs in the brain. MiRNAs were profiled by microarray, and differentially expressed miRNAs underwent target prediction and enrichment analysis. Microarray analysis revealed 56 differentially expressed miRNAs in AD mouse brain, which involved 39 miRNAs that were significantly upregulated and 19 that were downregulated at different ages. Among those miRNAs, a total of 11 miRNAs, including miR-342-3p, miR-342-5p, miR-376c-3p, and miR-301b-3p, were not only conserved in human but also predicted to have targets and signaling pathways closely related to the pathology of AD. In conclusion, in this study, differentially expressed miRNAs were identified in AD brain and proposed as biomarkers, which may have the potential to indicate AD progression. Despite being preliminary, these results may aid in investigating pathological hallmarks and identify effective therapeutic targets.

中文翻译：

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在阿尔茨海默氏病转基因小鼠模型中通过微阵列从大脑中分析microRNA。

微小RNA（miRNA）是小的非编码RNA，通过靶向mRNA进行裂解或翻译抑制来调节众多细胞功能，并且已发现其在阿尔茨海默氏病（AD）中起重要作用。我们的研究旨在鉴定AD脑中差异表达的miRNA，作为该疾病潜在治疗性miRNA或生物标记物的参考。我们使用淀粉样蛋白前体蛋白（APP）和早老素1（PS1）双转基因小鼠和年龄匹配的野生型（WT）同窝仔确定了miRNA在大脑中的表达。通过微阵列分析miRNA，并对差异表达的miRNA进行靶标预测和富集分析。芯片分析揭示了AD小鼠大脑中56个差异表达的miRNA，其中涉及39个在不同年龄显着上调的miRNA和19个在下调的miRNA。在这些miRNA中，包括miR-342-3p，miR-342-5p，miR-376c-3p和miR-301b-3p在内的总共11个miRNA不仅在人类中是保守的，而且还预测具有靶标和信号传导与AD病理密切相关的途径。总之，在这项研究中，差异表达的miRNA在AD脑中被鉴定出来，并被提议作为生物标志物，可能具有指示AD进展的潜力。尽管是初步的，但这些结果可能有助于研究病理学特征并确定有效的治疗靶标。它们不仅在人类中是保守的，而且还预测具有与AD病理学密切相关的靶标和信号传导途径。总之，在这项研究中，差异表达的miRNA在AD脑中被鉴定出来，并被提议作为生物标志物，可能具有指示AD进展的潜力。尽管是初步的，但这些结果可能有助于研究病理学特征并确定有效的治疗靶标。它们不仅在人类中是保守的，而且还预测具有与AD病理学密切相关的靶标和信号传导途径。总之，在这项研究中，差异表达的miRNA在AD脑中被鉴定出来，并被提议作为生物标志物，可能具有指示AD进展的潜力。尽管是初步的，但这些结果可能有助于研究病理学特征并确定有效的治疗靶标。