The production of amyloid β (Aβ) and tau hyperphosphorylation have been identified as key processes in Alzheimer’s disease (AD) pathogenesis. MiR-539-5p has been found to be abnormally expressed in brain tissue; however, the functional role of miR-539-5p in the pathogenesis of AD remains unclear. In our study, we found that the expression of miR-539-5p was significantly downregulated in humans and mice with AD and was negatively correlated with expression of APP, caveolin 1, and GSK-3β. Moreover, upregulation of miR-539-5p inhibited Aβ accumulation, tau phosphorylation, oxidative stress, and apoptosis and improved memory ability in AD mice. Furthermore, by using bioinformatics tool and dual-luciferase reporter assay, APP, Caveolin 1, and GSK-3β were confirmed as direct targets of miR-539-5p. In addition, the PI3K/AKT/GSK-3β signaling pathway can be regulated by miR-539-5p. In conclusion, this study provided a novel insight into the pathologic mechanism of AD by identifying that miR-539-5p plays a neuroprotective role in AD.

中文翻译：

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通过调节APP / PS1双转基因小鼠的PI3K / Akt /GSK-3β途径，MiR-539-5p减少淀粉样蛋白β的蛋白质生产，Tau的过度磷酸化和记忆障碍。

淀粉样蛋白β（Aβ）的产生和tau蛋白过度磷酸化已被确定为阿尔茨海默氏病（AD）发病机理的关键过程。已发现MiR-539-5p在脑组织中异常表达。然而，miR-539-5p在AD发病机理中的功能作用尚不清楚。在我们的研究中，我们发现miR-539-5p的表达在人和患有AD的小鼠中显着下调，并且与APP，caveolin 1和GSK-3β的表达负相关。此外，miR-539-5p的上调抑制了AD小鼠的Aβ积累，tau磷酸化，氧化应激和凋亡，并改善了记忆能力。此外，通过使用生物信息学工具和双荧光素酶报告基因测定，证实APP，Caveolin 1和GSK-3β是miR-539-5p的直接靶标。此外，PI3K / AKT /GSK-3β信号传导途径可被miR-539-5p调节。总之，这项研究通过鉴定miR-539-5p在AD中起神经保护作用，为AD的病理机制提供了新颖的见解。