Title:MiR-340 Reduces the Accumulation of Amyloid-β Through Targeting BACE1 (β-site Amyloid Precursor Protein Cleaving Enzyme 1) in Alzheimer’s Disease
VOLUME: 17 ISSUE: 1
Author(s):Xianpei Tan*, Yi Luo, Dingfang Pi, Liexin Xia, Zhilian Li and Qiang Tu
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
Keywords:miR-340, BACE1, amyloid-β, Alzheimer's disease, amyloid precursor protein (APPswe), neuronal cell.
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.
