Ji Yangfei, Wang Dan, Zhang Boai, Lu Hong
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Provence, 450001, P. R. China.
Department of Cardiology, Zhengzhou Central Hospital, Zhengzhou City, Henan Provence, 450001, P. R. China.
J Integr Neurosci. 2019 Sep 30;18(3):285-291. doi: 10.31083/j.jin.2019.03.1136.
The role of miR-361-3p in the pathology of Alzheimer's disease is unknown. The target scan was used to screen potential target genes of miR-361-3p, and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) was emphasized. Results from western blotting and reverse transcription-quantitative polymerase chain reaction (RT-PCR) showed that down-regulated miR-361-3p was correlated with up-regulated BACE1 in Alzheimer's disease patients' brains. Luciferase assay confirmed that miR-361-3p directly targets BACE1. MiR-361-3p overexpression and knockdown experiments were performed and found that miR-361-3p could regulate the expression of BACE1, and the accumulation of APP-β in APPswe transfected SH-SY5Y cell. A Morris water maze test was performed and showed that overexpression of miR-361-3p improved cognitive deficits in APP/PS1 mice. We found miR-361-3p inhibited β-amyloid accumulation by targeting BACE1, which thus weakened cognitive deficits in Alzheimer's disease.
miR-361-3p在阿尔茨海默病病理学中的作用尚不清楚。利用靶标扫描筛选miR-361-3p的潜在靶基因，其中β-位点淀粉样前体蛋白（APP）裂解酶1（BACE1）受到关注。蛋白质免疫印迹法和逆转录定量聚合酶链反应（RT-PCR）结果显示，阿尔茨海默病患者大脑中miR-361-3p表达下调与BACE1表达上调相关。荧光素酶报告基因检测证实miR-361-3p直接靶向BACE1。进行了miR-361-3p过表达和敲低实验，发现miR-361-3p可调节BACE1的表达以及APPswe转染的SH-SY5Y细胞中APP-β的积累。进行了莫里斯水迷宫试验，结果显示miR-361-3p过表达改善了APP/PS1小鼠的认知缺陷。我们发现miR-361-3p通过靶向BACE1抑制β-淀粉样蛋白的积累，从而减轻了阿尔茨海默病中的认知缺陷。
