Regulatory Mechanism of miR-543-3p on GLT-1 in a Mouse Model of Parkinson's Disease
Regulatory Mechanism of miR-543-3p on GLT-1 in a Mouse Model of Parkinson's Disease
复制标题
帕金森病小鼠模型中miR-543-3p对GLT-1的调控机制
DOI：
10.1021/acschemneuro.8b00683
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发表时间：
2019-03-01
影响因子：
5
通讯作者：
Qu, Shaogang
中科院分区：
文献类型：
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作者：
Wu, Xiaojuan;Meng, Xingjun;Qu, Shaogang
帕金森氏病（PD）的特征是黑质丘脑部多巴胺神经元的变性和死亡以及含有α-突触核蛋白的路易体的形成。在众多的PD病因中，谷氨酸兴奋毒性是研究的热点，而谷氨酸转运体在这一理论中起着关键作用。研究表明，谷氨酸转运蛋白的表达受microRNA的调控。在本研究中，我们发现在PD的发展过程中，谷氨酸转运蛋白1（GLT-1）的表达和功能水平显著降低，miR-543- 3 p上调。GLT-1在PD的发病机制中起重要作用。我们发现miR-543- 3 p可以抑制MPP+处理的星形胶质细胞和MPTP处理的小鼠中GLT-1的表达和功能。抑制miR-543- 3 p可以挽救GLT-1的表达和功能，并减轻PD模型中的运动障碍，这表明抑制miR-543- 3 p可以作为PD的潜在治疗靶点。
Parkinson's disease (PD) features the degeneration and death of dopamine neurons in the substantia nigra pars compacta and the formation of Lewy bodies that contain alpha-synuclein. Among the numerous PD etiologies, glutamate excitotoxicity is a research hot spot, and glutamate transporters play key roles in this theory. It has been shown that the expression of the glutamate transporter is regulated by microRNAs. In this study, we found that the levels of expression and function of glutamate transporter type 1 (GLT-1) were significantly reduced and miR-543-3p was upregulated during the development of PD. Furthermore, our results indicated that GLT-1 plays an important role in the pathomechanism of PD. We found that miR-543-3p can suppress the expression and function of GLT-1 in MPP+-treated astrocytes and MPTP-treated mice. Inhibition of miR-543-3p can rescue the expression and function of GLT-1 and relieve dyskinesia in the PD model, which suggests that inhibition of miR-543-3p could serve as a potential therapeutic target for PD.