MicroRNA-650 regulates the pathogenesis of Alzheimer’s Disease through targeting Cyclin-Dependent Kinase 5

Author:

Lin Li1ORCID,Liu Xiaodong1,Cheng Xuejun2,Li Yujing3,Gearing Marla3,Levey Allan3,Huang Xiaoli2,Li Ying2,Jin Peng3,Li Xuekun2

Affiliation:

1. Jinan University

2. Zhejiang University

3. Emory University

Abstract

Abstract Alzheimer’s disease (AD) pathogenesis features 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.

Publisher

Research Square Platform LLC

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