Central Laboratory and Department of Neurology, Shunde Hospital , Southern Medical University (The First People's Hospital of Shunde Foshan) , Foshan , 528300 , Guangdong , China.
Key Laboratory of Mental Health of the Ministry of Education , Southern Medical University , Guangzhou , 510515 , Guangdong , China.
ACS Chem Neurosci. 2019 Mar 20;10(3):1791-1800. doi: 10.1021/acschemneuro.8b00683. Epub 2019 Feb 7.
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 α-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.
帕金森病（PD）的特征是黑质致密部多巴胺神经元的退化和死亡，以及包含α-突触核蛋白的路易体的形成。在众多 PD 病因中，谷氨酸兴奋性毒性是一个研究热点，而谷氨酸转运体在该理论中起着关键作用。已经表明，谷氨酸转运体的表达受 microRNAs 调节。在这项研究中，我们发现 PD 发展过程中谷氨酸转运体 1（GLT-1）的表达和功能水平显著降低，miR-543-3p 上调。此外，我们的结果表明 GLT-1 在 PD 的发病机制中起重要作用。我们发现 miR-543-3p 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-543-3p 可以挽救 GLT-1 的表达和功能，并缓解 PD 模型中的运动障碍，这表明抑制 miR-543-3p 可能成为 PD 的潜在治疗靶点。
