4.6 Article

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

期刊

JOURNAL OF CELLULAR BIOCHEMISTRY
卷 120, 期 4, 页码 4942-4951

出版社

WILEY
DOI: 10.1002/jcb.27769

关键词

apoptosis; metastasis-associated lung adenocarcinoma transcript 1 (MALAT1); neurons; parkinson's disease (PD); resveratrol

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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.

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