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

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.

MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

“…We searched the literature (Kou et al, 2020; Patel et al, 2019; Sadlon et al, 2019) with the database (http://www.targetscan.org/vert_71/, Agarwal et al, 2015; http://starbase.sysu.edu.cn/index.php, J. H. Li et al, 2014) online analysis, the miRNAs associated with AD were intersected with miRNAs that targeted the POT1 3′‐UTR region in the database (Figure 4a), and the results showed that the intersection of the data in three databases was miR‐340‐5p. A previous study showed that miR‐340‐5p was downregulated in the hippocampus of AD model mice and reduced amyloid‐β accumulation by targeting BACE1 (Tan et al, 2020). The expression of miR‐340‐5p in AD mice and Aβ 42 ‐induced HT22 cells was detected by qRT‐PCR.…”

“…Increasingly, studies reported that miRNAs might be involved in the pathogenesis of AD (Kou et al, 2020; T. Li et al, 2020). miR‐340‐5p was downregulated in the hippocampus of AD model mice and reduced amyloid‐β accumulation by targeting BACE1 (Tan et al, 2020). In our study, bioinformatics analysis and dual‐luciferase reporter assay were performed to identify miRNAs that can target the telomere protection protein POT1 and finally found the targeted binding relationship between miR‐340‐5p and POT1.…”

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

“…MicroRNA-200a-3p also reduces the expression of BACE1 and is confirmed to be decreased in the hippocampus of APP/PS1 and SAMP8 mice as well as in blood plasma from AD patients (113). MicroRNA-340 is decreased in the hippocampus of an AD mouse model and associated with the overproduction of Aβ by targeting BACE1 (114). MicroRNA-31 reduces the mRNA levels of BACE1 and improves memory deficits in AD triple-transgenic (3xTg-AD) female mice (115).…”

Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

“…However, results solid for millions of mature patients affected by AD have failed to emerge. At the moment perspectives exist only for early stages of the disease [ 108 – 110 , 121 , 122 ].…”

“…Over-expression of a third, miR-340, has been shown to reduce the activity of presenilin 1, the most important enzyme for the generation of Aβ. The excess of miR-340 in brain cells reduces therefore the AD development [ 110 ].…”