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MiR-124 acts as a target for Alzheimer's disease by regulating BACE1
Fengmao An1,2, Guohua Gong1,2,3, Yu Wang1,2
1Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for The Nationalities, Tongliao, Inner Mongolia, P.R. China.
Abstract:
Although large numbers of microRNAs (miRNAs) expressed in Alzheimer disease (AD) have been detected, their functions and mechanisms of regulation remain to be fully clarified. Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) has been one of the prime therapeutic targets for AD. Here, we identified that miR-124 levels are gradually decreased in AD. In addition, we demonstrated that miR-124 suppresses BACE1 expression by directly targeting the 3'UTR of Bace1 mRNA in vitro. Inhibition of miR-124 significantly increased BACE1 levels in neuronal cells. In contrast, miR-124 overexpression significantly suppressed BACE1 expression in cells. And finally we determined that downregulation of miR-124 alleviated Aβ-induced viability inhibition and decreased apoptosis in SH-SY5Y cells. Our results demonstrated that miR-124 is a potent negative regulator of BACE1 in the cellular AD phenotype and might be involved in the pathogenesis of AD.
Insights
MicroRNA-124 (miR-124) levels decrease in Alzheimer disease (AD). This microRNA suppresses BACE1, a key therapeutic target, potentially impacting AD pathogenesis and offering new therapeutic avenues.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer disease (AD) pathogenesis involves complex molecular mechanisms.
- MicroRNAs (miRNAs) are implicated in AD, but their specific roles require further elucidation.
- Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is a critical therapeutic target in AD.
Purpose of the Study:
- To investigate the role of miR-124 in Alzheimer disease.
- To determine the regulatory relationship between miR-124 and BACE1.
- To assess the impact of miR-124 on cellular AD phenotypes.
Main Methods:
- Quantification of miR-124 levels in AD models.
- In vitro studies to assess miR-124 regulation of BACE1 expression via 3'UTR targeting.
- Manipulation of miR-124 levels (inhibition and overexpression) in neuronal cells.
- Assessment of cell viability and apoptosis in response to Aβ and miR-124 modulation.
Main Results:
- miR-124 levels were found to be decreased in Alzheimer disease.
- miR-124 directly targets the 3'UTR of Bace1 mRNA, suppressing BACE1 expression.
- Inhibition of miR-124 increased BACE1 levels, while overexpression decreased them.
- Downregulation of miR-124 ameliorated Aβ-induced viability inhibition and reduced apoptosis in SH-SY5Y cells.
Conclusions:
- miR-124 acts as a negative regulator of BACE1 in the context of Alzheimer disease.
- The miR-124/BACE1 axis is implicated in the cellular phenotype and pathogenesis of AD.
- miR-124 represents a potential therapeutic target for Alzheimer disease.