Downregulation of microRNA-15b-5p Targeting the Akt3-Mediated GSK-3β/β-Catenin Signaling Pathway Inhibits Cell Apoptosis in Parkinson's Disease.

Parkinson's disease (PD) is an incurable progressive disorder resulting from neurodegeneration, and apoptosis is considered a dominant mechanism underlying the process of neurodegeneration. MicroRNAs (miRNAs), which are small and noncoding RNAs involved in many a biological process like apoptosis an...

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Published in:BioMed Research International Vol. 2021; pp. 1 - 12
Main Authors: Jianzhong Zhu, Xue Xu, Yingyin Liang, Ronglan Zhu
Format: pictorial research tables/charts Journal Article
Published: Wiley-Blackwell 1/6/2021
Online Access:View this record in EBSCOhost
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      jtl: BioMed Research International
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      dt: 1/6/2021
      vid: 2021
      pid: 480
      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        148510168
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        10.1155/2021/8814862
        148510168
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      ppct: 11
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        atl: Downregulation of microRNA-15b-5p Targeting the Akt3-Mediated GSK-3β/β-Catenin Signaling Pathway Inhibits Cell Apoptosis in Parkinson's Disease.
      aug:
        au:
          Jianzhong Zhu
          Xue Xu
          Yingyin Liang
          Ronglan Zhu
        affil: Department of Neurology, Longmen County People's Hospital, Huizhou 516800, China
      sug:
        subj:
          Parkinson Disease
          MicroRNA
          Intracellular Signaling Peptides and Proteins
          Signal Transduction
          Apoptosis
          Gene Expression
          Protein Kinases
          In Vitro Studies
          In Vivo Studies
          Flow Cytometry
          Spectrophotometry
          Caspases
          Reverse Transcriptase Polymerase Chain Reaction
          Blotting, Western
      ab: Parkinson's disease (PD) is an incurable progressive disorder resulting from neurodegeneration, and apoptosis is considered a dominant mechanism underlying the process of neurodegeneration. MicroRNAs (miRNAs), which are small and noncoding RNAs involved in many a biological process like apoptosis and regulation of gene expressions, have been found in postmortem brain samples of patients with PD, as well as in vitro and in vivo models of PD. To explore the impact of miR-15b-5p and Akt3 on apoptosis in the progression of PD, the method of quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed, and the analysis result showed upregulated expression of miR-15b-5p and downregulated expression of Akt3 in the serum of PD patients, MPP+-induced SH-SY5Y cells, and the brain tissues of MPTP-induced mice. Meanwhile, the dualluciferase reporter assay was used to demonstrate the regulator-target interaction between miR-15b-5p and Akt3; flow cytometry and spectrophotometry revealed that transfection of miR-15b-5p mimic and si-Akt3 increased the rate of apoptosis and caspase-3 activity, whereas transfecting the miR-15b-5p inhibitor and Akt3-overexpression plasmid repressed the rate of apoptosis and caspase-3 activity in the MPP+-induced SH-SY5Y cell model and the MPTP-induced mouse model. Additionally, analysis of western blotting (WB) assays in vivo and in vitro revealed that proapoptosis proteins (Bax, caspase-3, GSK-3β, and β-catenin) showed markedly upregulated expression in the miR-15b-5p inhibitor and si-Akt3-overexpression groups, while the expression of an antiapoptosis gene (i.e., Bcl2) was downregulated. These analysis results indicate that downregulation of miR-15b-5p by targeting the Akt3-mediated GSK-3β/β-catenin signaling pathway would repress cell apoptosis in PD in vivo and in vitro. It is expected that the research findings would help find new therapeutic targets for treatment of PD.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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