MicroRNA-650 Regulates the Pathogenesis of Alzheimer's Disease Through Targeting Cyclin-Dependent Kinase 5
Li Lin1, Xiaodong Liu2, Xuejun Cheng3,4
1Guangdong-Hongkong-Macau Institute of CNS Regeneration, Guangdong Key Laboratory of Nonhuman Primate Models of Human Diseases, Key Laboratory of CNS Regeneration (Ministry of Education), Jinan University, Guangzhou, 510632, China. linli@jnu.edu.cn.
Abstract:
Alzheimer's disease (AD) pathogenesis feature progressive neurodegeneration, amyloid-β plaque formation, and neurofibrillary tangles. Ample evidence has indicated the involvement of epigenetic pathways in AD pathogenesis. Here, we show that the expression of microRNA 650 (miR-650) is altered in brains from AD patients. Furthermore, we found that the processing of primary miR-650 to mature miR-650 is misregulated. Bioinformatic analysis predicted that miR-650 targets the expression of three AD-associated components: Apolipoprotein E (APOE), Presenilin 1 (PSEN1), and Cyclin-Dependent Kinase 5 (CDK5), and we have experimentally confirmed that miR-650 is able to significantly reduce the expression of APOE, PSEN1, and CDK5 in vitro. Importantly, the overexpression of miR-650 was further shown to significantly alter the CDK5 level and ameliorate AD pathologies in APP-PSEN1 transgenic mice. Overall, our results indicate that miR-650 influences AD pathogenesis through regulation of CDK5.
Insights
MicroRNA 650 (miR-650) is dysregulated in Alzheimer's disease (AD). This study shows miR-650 regulates Cyclin-Dependent Kinase 5 (CDK5), offering a potential therapeutic target for AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) involves neurodegeneration and epigenetic pathway dysregulation.
- MicroRNAs (miRNAs) are implicated in AD pathogenesis.
- Specific miRNA alterations in AD brains require further investigation.
Purpose of the Study:
- To investigate the role of microRNA 650 (miR-650) in Alzheimer's disease (AD).
- To identify miR-650 targets relevant to AD pathology.
- To evaluate the therapeutic potential of modulating miR-650 in AD.
Main Methods:
- Analysis of miR-650 expression and processing in AD patient brains.
- Bioinformatic prediction and in vitro validation of miR-650 targets (APOE, PSEN1, CDK5).
- In vivo studies using APP-PSEN1 transgenic mice to assess miR-650 overexpression effects on AD pathology.
Main Results:
- miR-650 expression and processing are misregulated in Alzheimer's disease (AD) brains.
- miR-650 directly targets and reduces the expression of Apolipoprotein E (APOE), Presenilin 1 (PSEN1), and Cyclin-Dependent Kinase 5 (CDK5) in vitro.
- Overexpression of miR-650 in APP-PSEN1 mice altered CDK5 levels and ameliorated AD pathologies.
Conclusions:
- miR-650 plays a significant role in Alzheimer's disease (AD) pathogenesis.
- Regulation of Cyclin-Dependent Kinase 5 (CDK5) by miR-650 is a key mechanism.
- miR-650 represents a potential therapeutic target for Alzheimer's disease (AD).
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