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,China
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.
