MiR-361-3p inhibits β-amyloid accumulation and attenuates cognitive deficits through targeting BACE1 in Alzheimer's disease
MiR-361-3p inhibits β-amyloid accumulation and attenuates cognitive deficits through targeting BACE1 in Alzheimer's disease
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DOI：
10.31083/j.jin.2019.03.1136
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发表时间：
2019-09-30
影响因子：
1.8
通讯作者：
Lu, Hong
中科院分区：
文献类型：
--
作者：
Ji, Yangfei;Wang, Dan;Lu, Hong
miR-361- 3 p在阿尔茨海默病病理学中的作用尚不清楚。采用靶点扫描法筛选miR-361- 3 p的潜在靶基因，重点研究β位点淀粉样前体蛋白（APP）裂解酶1（BACE 1）。Western blotting和逆转录-定量聚合酶链反应（RTPCR）结果显示，阿尔茨海默病患者脑中miR-361- 3 p的下调与BACE 1的上调相关。荧光素酶测定证实miR-361- 3 p直接靶向BACE 1。通过miR-361- 3 p过表达和敲低实验，发现miR-361- 3 p可以调节BACE 1的表达，并能抑制APP-β在转染细胞中的积累。进行Morris水迷宫测试，结果显示miR-361- 3 p的过表达改善了APP/PS1小鼠的认知缺陷。我们发现miR-361- 3 p通过靶向BACE 1抑制β-淀粉样蛋白积累，从而削弱阿尔茨海默病的认知缺陷。
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 beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) was emphasized. Results from western blotting and reverse transcription-quantitative polymerase chain reaction (RTPCR) 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-beta 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 beta-amyloid accumulation by targeting BACE1, which thus weakened cognitive deficits in Alzheimer's disease.