The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression
1Department of Neurology, The Second Hospital of Shandong University, Shandong University, 247 North Park Avenue, Jinan, 250033, China.
BMC Molecular Biology
|October 2, 2019
Summary
The long noncoding RNA BACE1-AS promotes amyloid-beta (Aβ) generation in Alzheimer's disease models. Silencing BACE1-AS reduced Aβ production, indicating its role in disease pathogenesis.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- BACE1-AS is a conserved long noncoding RNA (lncRNA) implicated in Alzheimer's disease (AD).
- Elevated BACE1-AS and BACE1 mRNA levels are observed in AD subjects.
- BACE1-AS modulates BACE1 mRNA expression and promotes amyloid-beta (Aβ) formation.
Purpose of the Study:
- To investigate the role of BACE1-AS in regulating BACE1 expression and Aβ generation.
- To determine if BACE1-AS mediates the effects of exogenous Aβ on BACE1 expression and Aβ production.
Main Methods:
- Administration of Aβ1-42 to SH-SY5Y cells and C57BL/6J mice.
- Detection of BACE1-AS, BACE1 mRNA, BACE1 protein, and Aβ1-40 levels.
- Silencing of BACE1-AS using siRNAs in cell lines.
Main Results:
- Aβ1-42 administration increased BACE1-AS, BACE1 mRNA, BACE1 protein, and Aβ1-40 levels in cells and mice.
- BACE1-AS siRNA pretreatment inhibited Aβ1-42-induced increases in BACE1-AS, BACE1, and Aβ generation.
- BACE1-AS silencing reduced BACE1 mRNA and protein levels and Aβ1-40 generation.
Conclusions:
- Exogenous Aβ1-42 induces BACE1 expression and Aβ generation via BACE1-AS.
- BACE1-AS is a key mediator in the regulatory mechanism of BACE1 expression and Aβ generation.
- BACE1-AS plays a role in APPsw transgenic cells for BACE1 expression and Aβ generation.
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