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Potential Regulatory Role of miR-21 on Alzheimer's Disease by Targeting GSK-3β Signaling
1Henan Vocational College of Industry and Trade, Zhengzhou 450000, China.
Background:
Alzheimer's disease (AD) is the most important neurogenerative disorder with progressive dementia as its main clinical manifestation. The microRNAs (miRNAs) are identified as crucial modulators in AD progression. Nevertheless, the biological potential of miR-21 in AD is obscure. Hence, this study aimed to evaluate the possible role of miR-21 in the pathogenesis of AD via phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta (GSK-3β) signaling.
Materials And Methods:
The miR-21 expression in the brain tissues of patients with AD, as well as normal brain tissues and Aβ1-42-stimulated SH-SY5Y cell line (AD model) was examined by in situ hybridization and quantitative real-time polymerase chain reaction. Also, the apoptosis-linked protein levels as well as programmed cell death 4 (PDCD4) were detected by western blot.
Results:
Our findings revealed that miR-21 was low expressed in the brain tissues of patients with AD and AD model (P0.01). Also, the miR-21 overexpression could inhibit apoptosis of the AD model (P0.01). Indeed, the miR-21 negatively regulated PDCD4 expression, which led to activated PI3K/AKT/GSK-3β signaling.
Conclusion:
Our study demonstrated that miR-21 cloud inhibits cell apoptosis in AD through the activation of PI3K/AKT/GSK-3β signaling pathway using inhibition of PDCD4 expression.
Insights
MicroRNA-21 (miR-21) is downregulated in Alzheimer's disease (AD), where its overexpression inhibits apoptosis by activating the PI3K/AKT/GSK-3β pathway through PDCD4 inhibition.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is a leading cause of neurodegenerative dementia.
- MicroRNAs (miRNAs) play a role in AD pathogenesis, but miR-21's function is unclear.
- This study investigates miR-21's role in AD via the PI3K/AKT/GSK-3β pathway.
Purpose of the Study:
- To evaluate the role of miR-21 in Alzheimer's disease pathogenesis.
- To investigate the effect of miR-21 on apoptosis in an AD cellular model.
- To explore the involvement of the PI3K/AKT/GSK-3β signaling pathway.
Main Methods:
- Examined miR-21 expression in AD brain tissues and an in vitro AD model using in situ hybridization and qPCR.
- Assessed apoptosis-related proteins and PDCD4 levels via Western blot.
- Investigated the impact of miR-21 on the PI3K/AKT/GSK-3β pathway.
Main Results:
- miR-21 expression was significantly lower in AD brain tissues and the AD model.
- Overexpression of miR-21 reduced apoptosis in the AD model.
- miR-21 negatively regulated PDCD4, leading to activation of the PI3K/AKT/GSK-3β pathway.
Conclusions:
- miR-21 inhibits apoptosis in Alzheimer's disease.
- This effect is mediated by the PI3K/AKT/GSK-3β signaling pathway.
- miR-21's protective role involves the inhibition of programmed cell death 4 (PDCD4).
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