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白藜芦醇通过调节 MALAT1/miR-129/SNCA 信号通路抑制神经元凋亡改善帕金森病样表型。

Administration of resveratrol improved Parkinson's disease-like phenotype by suppressing apoptosis of neurons via modulating the MALAT1/miR-129/SNCA signaling pathway.

机构信息

Department of Neurosurgery, The First Affiliated Hospital to Jinzhou Medical University, Jinzhou, Liaoning, China.

Department of Neurology, The First Affiliated Hospital to Jinzhou Medical University, Jinzhou, Liaoning, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):4942-4951. doi: 10.1002/jcb.27769. Epub 2018 Sep 27.

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in the pathogenesis of Parkinson's disease (PD). In addition, resveratrol was shown to regulate the expression of MALAT1. Therefore, the objective of this study was to clarify the role of resveratrol in PD. During the study, luciferase assays were conducted to determine the effect of resveratrol on the transcription efficiency of MALAT1 promoter as well as the regulatory relationships among MALAT1, miR-129, and SNCA. In addition, real-time PCR, Western blot analysis, MTT and flow cytometry analyses were conducted to investigate the mechanism of resveratrol in PD. Furthermore, a PD mouse model was established to study the role of resveratrol in vivo. It was found that resveratrol increased the number of TH+ cells and the expression of miR-129, while decreasing the expression of MALAT1 and SNCA. In addition, MALAT1 inhibited the expression of miR-129, a negative regulator of SNCA, thus increasing the expression of SNCA. A further mechanistic study revealed that resveratrol inhibited MALAT1 expression by blocking the transcription of the MALAT1 promoter. Finally, MPTP treatment could decrease cell proliferation and increase cell apoptosis, while resveratrol could partly offset the effect of MPTP. In summary, the therapeutic effect of resveratrol in the treatment of PD can be attributed to its ability to modulate the MALAT1/miR-129/SNCA signaling pathway.

摘要

转移相关肺腺癌转录物 1(MALAT1)已被牵连到帕金森病(PD)的发病机制中。此外,白藜芦醇被证明可以调节 MALAT1 的表达。因此,本研究的目的是阐明白藜芦醇在 PD 中的作用。在研究过程中,进行了荧光素酶测定,以确定白藜芦醇对 MALAT1 启动子转录效率的影响,以及 MALAT1、miR-129 和 SNCA 之间的调控关系。此外,还进行了实时 PCR、Western blot 分析、MTT 和流式细胞术分析,以研究白藜芦醇在 PD 中的作用机制。此外,建立了 PD 小鼠模型,以研究白藜芦醇在体内的作用。结果发现,白藜芦醇增加了 TH+细胞的数量和 miR-129 的表达,同时降低了 MALAT1 和 SNCA 的表达。此外,MALAT1 抑制了 miR-129 的表达,miR-129 是 SNCA 的负调节剂,从而增加了 SNCA 的表达。进一步的机制研究表明,白藜芦醇通过阻断 MALAT1 启动子的转录来抑制 MALAT1 的表达。最后,MPTP 处理可降低细胞增殖并增加细胞凋亡,而白藜芦醇可部分抵消 MPTP 的作用。总之,白藜芦醇在治疗 PD 中的治疗效果可归因于其调节 MALAT1/miR-129/SNCA 信号通路的能力。

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