MiR-130a-3p Has Protective Effects in Alzheimer's Disease via Targeting DAPK1
Yanbo Wang1, Min Shi1, Zhenmei Hong1
1Department of Neurology, The Third Affiliated Hospital of Zhejiang Chinese Medicine University, Zhejiang, China.
Abstract:
The present study investigated the role and potential mechanisms of miR-130a-3p in AD. SH-SY5Y cells were treated with Aβ 1-42 to construct AD cell models. APP/PS1 mice were used for the animal experiments. MiR-130a-3p was downregulated in Aβ-induced SH-SY5Y cells. Overexpression of miR-130a-3p attenuates Aβ induced SH-SY5Y cell apoptosis. Low miR-130a-3p expression was detected in the hippocampus tissues of AD mice. The Morris water maze (MWM) results indicated that miR-130a-3p upregulation reduced the escape latency time and increased the time of AD mice spent in the target quadrant. DAPK1 was the target gene of miR-130a-3p. High DAPK1 mRNA level was detected in Aβ treated PC 12 cells and in the hippocampus tissues of AD mice. It was concluded that overexpression of miR-130a-3p may attenuate Aβ-induced neurotoxicity and improve the cognitive function of AD mice via targeting DAPK1.
Insights
MicroRNA-130a-3p (miR-130a-3p) is reduced in Alzheimer's disease (AD) models. Restoring miR-130a-3p levels may protect against neurotoxicity and improve cognitive function in AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression and are implicated in AD pathogenesis.
- miR-130a-3p dysregulation is observed in neurological conditions.
Purpose of the Study:
- To investigate the role of miR-130a-3p in Alzheimer's disease.
- To elucidate the potential mechanisms underlying miR-130a-3p's function in AD.
- To assess the therapeutic potential of modulating miR-130a-3p in AD models.
Main Methods:
- Established Alzheimer's disease cell models using SH-SY5Y cells treated with amyloid-beta (Aβ) 1-42.
- Utilized APP/PS1 transgenic mice for in vivo animal experiments.
- Assessed cell apoptosis, cognitive function using the Morris water maze (MWM), and gene expression levels.
Main Results:
- miR-130a-3p was significantly downregulated in Aβ-treated cells and AD mouse hippocampus.
- Overexpression of miR-130a-3p reduced Aβ-induced apoptosis in SH-SY5Y cells.
- Upregulation of miR-130a-3p improved cognitive performance in AD mice, indicated by reduced escape latency and increased target quadrant exploration.
- DAPK1 was identified as a direct target gene of miR-130a-3p, with high DAPK1 mRNA levels observed in AD models.
Conclusions:
- miR-130a-3p plays a protective role against Aβ-induced neurotoxicity.
- Modulating miR-130a-3p may offer a therapeutic strategy for Alzheimer's disease.
- The protective effects of miR-130a-3p are mediated, at least in part, through the regulation of DAPK1.
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