MiR-340 Reduces the Accumulation of Amyloid-β Through Targeting BACE1 (β-site Amyloid Precursor Protein Cleaving Enzyme 1) in Alzheimer's Disease
| Autor: | Zhilian Li, Ding-Fang Pi, Liexin Xia, Yi Luo, Xianpei Tan, Qiang Tu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Amyloid Down-Regulation Hippocampus Flow cytometry Cell Line 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Developmental Neuroscience Western blot Alzheimer Disease Cell Line Tumor mental disorders medicine Amyloid precursor protein Animals Aspartic Acid Endopeptidases Humans Neurons Reporter gene Amyloid beta-Peptides medicine.diagnostic_test biology Chemistry Transfection Molecular biology In vitro Disease Models Animal MicroRNAs 030104 developmental biology Neurology Apoptosis biology.protein Amyloid Precursor Protein Secretases 030217 neurology & neurosurgery |
| Zdroj: | Current neurovascular research. 17(1) |
| ISSN: | 1875-5739 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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