MiR-124 acts as a target for Alzheimer's disease by regulating BACE1.
MiR-124 acts as a target for Alzheimer's disease by regulating BACE1.
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MiR-124 通过调节 BACE1 充当阿尔茨海默病的靶标
DOI：
10.18632/oncotarget.23119
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发表时间：
2017-12-26
期刊：
影响因子：
--
通讯作者：
Wei C
中科院分区：
文献类型：
--
作者：
An F;Gong G;Wang Y;Bian M;Yu L;Wei C
虽然在阿尔茨海默病（AD）中已经发现了大量表达的microRNAs (miRNAs)，但它们的功能和调控机制尚不完全清楚。β位点淀粉样蛋白前体蛋白切割酶1 （BACE1）已成为阿尔茨海默病的主要治疗靶点之一。在这里，我们发现miR-124水平在AD中逐渐降低。此外，我们在体外证明了miR-124通过直接靶向BACE1 mRNA的3'UTR抑制BACE1的表达。抑制miR-124显著增加神经元细胞中BACE1的水平。相反，miR-124过表达可显著抑制细胞中BACE1的表达。最后，我们确定miR-124的下调减轻了a β诱导的SH-SY5Y细胞活力抑制和减少凋亡。我们的研究结果表明，miR-124是细胞AD表型中BACE1的有效负调节因子，可能参与AD的发病机制。
Although large numbers of microRNAs (miRNAs) expressed in Alzheimer disease (AD) have been detected, their functions and mechanisms of regulation remain to be fully clarified. Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) has been one of the prime therapeutic targets for AD. Here, we identified that miR-124 levels are gradually decreased in AD. In addition, we demonstrated that miR-124 suppresses BACE1 expression by directly targeting the 3′UTR of Bace1 mRNA in vitro. Inhibition of miR-124 significantly increased BACE1 levels in neuronal cells. In contrast, miR-124 overexpression significantly suppressed BACE1 expression in cells. And finally we determined that downregulation of miR-124 alleviated Aβ-induced viability inhibition and decreased apoptosis in SH-SY5Y cells. Our results demonstrated that miR-124 is a potent negative regulator of BACE1 in the cellular AD phenotype and might be involved in the pathogenesis of AD.
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影响因子：
64.5
作者：
Hatziapostolou M;Polytarchou C;Aggelidou E;Drakaki A;Poultsides GA;Jaeger SA;Ogata H;Karin M;Struhl K;Hadzopoulou-Cladaras M;Iliopoulos D
通讯作者：
Iliopoulos D
DOI：
10.1523/jneurosci.0558-12.2012
发表时间：
2012-06-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Åkerblom M;Sachdeva R;Barde I;Verp S;Gentner B;Trono D;Jakobsson J
通讯作者：
Jakobsson J
影响因子：
10.7
作者：
Moore, D. Blaine;Gillentine, Madelyn A.;Langeland, James A.
通讯作者：
Langeland, James A.
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
4
作者：
Femminella GD;Ferrara N;Rengo G
通讯作者：
Rengo G