Department of Neurology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, China.
Department of Neurology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, China,
Neuroimmunomodulation. 2019;26(4):174-187. doi: 10.1159/000501339. Epub 2019 Aug 27.
Recent studies have elaborated on the concept that a number of microRNAs (miRNAs) have a potential effect on the pathogenesis and development of Parkinson's disease (PD). PD is recognized as a common progressive bradykinetic disorder that results from the death of dopaminergic neurons in the substantia nigra. The purpose of this study was to explore whether microRNA-124 (miR-124) affected dopamine receptor (DAR) expression and neuronal proliferation and apoptosis in the 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models of PD. The targeting relationship of miR-124 and EDN2 was confirmed through bioinformatic predictions and dual-luciferase reporter assay. The expression of miR-124 and EDN2 was altered to assess their effect on the expression of DAR in the substantia nigra and isolated neurons, as well as the neuronal proliferation and apoptosis rate. The obtained results implied that the treatments of miR-124 mimic and si-EDN2 resulted in elevated expressions of Glil, SHH, PTCH1, DAT, DRD1, and DRD2. However, these treatments facilitated neuronal proliferation and suppressed neuronal apoptosis, corresponding to reduced expression of caspase-3 and Bax, as well as increased levels of Bcl-2 expression. These results were discovered to be achieved through the activation of the Hedgehog signaling pathway. With this taken into account, our study demonstrated that miR-124 overexpression promoted DAR expression and neuronal proliferation and suppressed neuronal apoptosis by downregulating EDN2 via activating the Hedgehog signaling pathway.
最近的研究详细阐述了这样一个概念，即许多 microRNAs（miRNAs）可能对帕金森病（PD）的发病机制和发展有潜在影响。PD 被认为是一种常见的进行性运动迟缓障碍，是由于黑质中多巴胺能神经元的死亡引起的。本研究旨在探讨 microRNA-124（miR-124）是否影响 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 小鼠模型中多巴胺受体（DAR）的表达以及神经元增殖和凋亡。通过生物信息学预测和双荧光素酶报告基因检测证实了 miR-124 与 EDN2 的靶向关系。改变 miR-124 和 EDN2 的表达，评估它们对黑质和分离神经元中 DAR 表达以及神经元增殖和凋亡率的影响。结果表明，miR-124 模拟物和 si-EDN2 的处理导致 Glil、SHH、PTCH1、DAT、DRD1 和 DRD2 的表达升高。然而，这些处理促进了神经元的增殖，抑制了神经元的凋亡，对应于 caspase-3 和 Bax 的表达减少，以及 Bcl-2 表达的增加。这些结果是通过激活 Hedgehog 信号通路实现的。考虑到这一点，我们的研究表明，miR-124 通过下调 EDN2 激活 Hedgehog 信号通路，促进 DAR 表达、神经元增殖和抑制神经元凋亡。
