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

[ Vol. 17 , Issue. 1 ]

Author(s):

Xianpei Tan*, Yi Luo, Dingfang Pi, Liexin Xia, Zhilian Li and Qiang Tu   Pages 86 - 92 ( 7 )

Abstract:


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

Methods: The expression of miR-340 in senescence-accelerated mouse prone-8 (SAMP8) mouse and senescence-accelerated mice/resistant-1 (SAMR1) mouse was evaluated by qRT-PCR (quantitative real-time polymerase chain reaction). The 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 the 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 the accumulation of amyloid-β and suppressed cell apoptosis through targeting BACE1 in SH-SY5Y/APPswe cells.

Conclusion: MiR-340 was downregulated in AD and reduced the accumulation of amyloid-β through targeting BACE1, suggesting a potential therapeutic target for AD.

Keywords:

miR-340, BACE1, amyloid-β, Alzheimer's disease, amyloid precursor protein (APPswe), neuronal cell.

Affiliation:

Department of Neurology, Jingzhou First People’s Hospital, The First Affiliated Hospital of Yangtze University, Jingzhou City, Hubei Province, 434000, Department of Neurology, Jingzhou First People’s Hospital, The First Affiliated Hospital of Yangtze University, Jingzhou City, Hubei Province, 434000, Department of Neurology, Jingzhou First People’s Hospital, The First Affiliated Hospital of Yangtze University, Jingzhou City, Hubei Province, 434000, Department of Neurology, Jingzhou First People’s Hospital, The First Affiliated Hospital of Yangtze University, Jingzhou City, Hubei Province, 434000, Department of Neurology, Jingzhou First People’s Hospital, The First Affiliated Hospital of Yangtze University, Jingzhou City, Hubei Province, 434000, Department of Neurology, Jingzhou First People’s Hospital, The First Affiliated Hospital of Yangtze University, Jingzhou City, Hubei Province, 434000



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