miR-340 Reduces the Accumulation of amyloid-β through Targeting BACE1 (β-site Amyloid Precursor Protein Cleaving Enzyme 1) in Alzheimer’ s Disease

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Author(s): Xianpei Tan*, Yi Luo, Dingfang Pi, Liexin Xia, Zhilian Li, Qiang Tu.

Journal Name: Current Neurovascular Research

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Background: Alzheimer’ s disease (AD) is the most common neurodegenerative disease, and accumulation of amyloid-β is the initial process in AD. MicroRNAs (miRNAs) are widely known as key regulator of accumulation of amyloid-β in AD. This study analyzed the potential effects and possible internal mechanism of miR-340 on AD.

Methods: Expression of miR-340 in senescence accelerated mouse prone-8 (SAMP8) mouse and senescence accelerated mice/resistant-1 (SAMR1) mouse were evaluated by qRT-PCR (quantitative real-time polymerase chain reaction). Expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) was determined by qRT-PCR and western blot. The binding ability between miR-340 and BACE1 was verified by dual‑luciferase reporter assay. In vitro cell model of AD was established in human neuroblastoma SH-SY5Y cells transfected with Swedish mutant form of amyloid precursor protein (APPswe). The effect of miR-340 on accumulation of amyloid-β was investigated by western blot analysis. Flow cytometry was conducted to detect cell apoptosis.

Results: MiR-340 was down-regulated in the hippocampus of AD model SAMP8 mouse compared to SAMR1 mouse, while BACE1 was up-regulated in SAMP8, suggesting a negative correlation between miR-340 and BACE1 in SAMP8 mouse. MiR-340 could directly bind with BACE1, and over-expression of miR-340 decreased expression of BACE1 in SH-SY5Y/APPswe cells. MiR-340 reduced accumulation of amyloid-β and suppressed cell apoptosis through targeting BACE1 in SH-SY5Y/APPswe cells.

Conclusion: MiR-340 was down-regulated in AD and educed accumulation of amyloid-βthrough targeting BACE1, suggesting a potential therapeutic target for AD.

Keywords: miR-340, BACE1, amyloid-β, Alzheimer’ s disease, Alzheimer’ s disease (AD), Amyloid precursor protein (APPswe)

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(E-pub Ahead of Print)
DOI: 10.2174/1567202617666200117103931
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