Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Brain Res Bull. 2012 Sep 1;88(6):596-601. doi: 10.1016/j.brainresbull.2012.05.018. Epub 2012 Jun 19.
Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by amyloid-beta (Aβ) deposition and neurofibrillary tangles. Numerous microRNAs have been found to play crucial roles in regulating Aβ production in the process of AD. Previous investigations have reported lower levels of many microRNAs in AD patients and animal models. Here, we examined the role of miR-195 in the process of Aβ formation. Bioinformatics' algorithms predicted miR-195 binding sites within the beta-site APP cleaving enzyme 1 (BACE1) 3'-untranslated region (3'-UTR), and we found the level of miR-195 to be negatively related to the protein level of BACE1 in SAMP8 mice. We confirmed the target site in HEK293 cells by luciferase assay. Overexpression of miR-195 in N2a/WT cells decreased the BACE1 protein level, and inhibition of miR-195 resulted in increase of BACE1 protein level. Furthermore, overexpression of miR-195 in N2a/APP decreased the level of Aβ, while inhibition of miR-195 resulted in an increase of Aβ. Thus, we demonstrated that miR-195 could downregulate the level of Aβ by inhibiting the translation of BACE1. We conclude that miR-195 might provide a therapeutic strategy for AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是淀粉样蛋白-β（Aβ）沉积和神经原纤维缠结。大量的 microRNA 被发现在 AD 发生过程中在调节 Aβ 产生方面发挥着关键作用。先前的研究报道 AD 患者和动物模型中的许多 microRNA 水平较低。在这里，我们研究了 miR-195 在 Aβ 形成过程中的作用。生物信息学算法预测了 miR-195 在β位淀粉样前体蛋白水解酶 1（BACE1）3'-非翻译区（3'-UTR）内的结合位点，我们发现 miR-195 的水平与 SAMP8 小鼠中 BACE1 的蛋白水平呈负相关。我们通过荧光素酶测定法在 HEK293 细胞中证实了靶位。在 N2a/WT 细胞中过表达 miR-195 降低了 BACE1 蛋白水平，而抑制 miR-195 则导致 BACE1 蛋白水平升高。此外，在 N2a/APP 中过表达 miR-195 降低了 Aβ 的水平，而抑制 miR-195 则导致 Aβ 水平升高。因此，我们证明 miR-195 可以通过抑制 BACE1 的翻译来下调 Aβ 的水平。我们得出结论，miR-195 可能为 AD 提供一种治疗策略。
