谷氨酸转运体在帕金森病发病机制中作用的研究进展

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (12): 1813-1817.

谷氨酸转运体在帕金森病发病机制中作用的研究进展

马利芳¹, 梁建庆^1,2*, 何建成³, 孙雪¹, 梁鹏⁴

1.甘肃中医药大学基础医学院, 甘肃兰州 730000;
2.甘肃中医药大学敦煌医学与转化教育部重点实验室,甘肃兰州 730000;
3.上海中医药大学基础医学院, 上海 201203;
4.兰州大学第二临床医学院, 甘肃兰州 730000

收稿日期:2021-03-29 修回日期:2021-07-09 发布日期:2021-12-03
通讯作者: *1766424015@qq.com
基金资助:
国家自然科学基金(81573899,82160929,81660767);甘肃省教育厅青年博士基金(2021QB-077);敦煌医学与转化省部共建教育部重点实验室开放课题(DHYX18-08);甘肃省中医药研究中心专项开放课题(zyzx-2020-zx20)

Research progress on the role of glutamate transporter in the pathogenesis of Parkinson's disease

MA Li-fang¹, LIANG Jian-qing^1,2*, HE Jian-cheng³, SUN Xue¹, LIANG Peng⁴

1. School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000;2. the Key Laboratory of the Ministry of Education of Dunhuang Medicine and Transformation, Gansu University of Traditional Chinese Medicine, Lanzhou 730000;
3. School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203;
4. the Second Clinical Medical College, Lanzhou University, Lanzhou 730000,China

Received:2021-03-29 Revised:2021-07-09 Published:2021-12-03
Contact: *1766424015@qq.com

摘要/Abstract

摘要： 谷氨酸(Glu)介导的兴奋性毒性是帕金森病(PD)的主要发病机制,其中谷氨酸转运体是调控Glu兴奋性毒性过程的关键因子,故而谷氨酸转运体可能参与PD的发病并在其过程中发挥着重要作用。因此,了解谷氨酸转运体在PD发病机制中的作用,有助于后期为以谷氨酸转运体为靶点的药物研发提供新的思路。

关键词: 帕金森病, 谷氨酸, 谷氨酸转运体, EAATs, VGLUTs

Abstract: The excitotoxicity mediated by glutamate (Glu) is the main pathogenesis of Parkinson’s disease (PD), and the glutamate transporter is the key factor regulating the process of Glu excitotoxicity. Therefore, glutamate transporters may be involved in the pathogenesis of PD and play an important role in the process. Therefore, understanding the role of glutamate transporters in the pathogenesis of PD may provide new ideas for later drug research and development targeting at glutamate transporters.

Key words: Parkinson&apos, s disease, glutamate, glutamate transporter, excitatory amino acid transporters (EAATs), vesicular glutamate transporters (VGLUTs)

中图分类号:

R741

马利芳, 梁建庆, 何建成, 孙雪, 梁鹏. 谷氨酸转运体在帕金森病发病机制中作用的研究进展[J]. 基础医学与临床, 2021, 41(12): 1813-1817.

MA Li-fang, LIANG Jian-qing, HE Jian-cheng, SUN Xue, LIANG Peng. Research progress on the role of glutamate transporter in the pathogenesis of Parkinson's disease[J]. Basic & Clinical Medicine, 2021, 41(12): 1813-1817.

参考文献

[1]Dong Y, Xiong M, Chen Y, et al.Plasticity of synaptic transmission in human stem cell-derived neural networks[J].iScience, 2020, 23:100829-100854.
[2]Wu X, Meng X, Tan F, et al.Regulatory mechanism of miR-543-3p on GLT-1 in a mouse model of Parkinson's Disease[J].ACS Chem Neurosci, 2019, 10:1791-1800.
[3]Du X, Li J, Li M, et al.Research progress on the role of type I vesicular glutamate transporter (VGLUT1) in nervous system diseases[J].Cell Biosci, 2020, 10:26-36.
[4]Todd AC, Hardingham GE.The regulation of astrocytic glutamate transporters in health and neurodegenerative diseases[J].Int J Mol Sci, 2020, 21:9607-9637.
[5]Kanai Y, Hediger MA.Primary structure and functional characterization of a high-affinity glutamate transporter[J].Nature, 1992, 360:467-471.
[6]Zhang Y, He X, Meng X, et al.Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model[J].Cell Death Dis, 2017, 8:e2574-e2587.
[7]晏义平, 孙凤艳. 谷氨酸转运体的结构和功能[J].生命科学, 1999, 1:20-22.
[8]米超, 杨欣欣, 齐志鹏, 等. 利鲁唑上调EAATs产生对MPTP诱导的帕金森模型小鼠的保护作用[J].实用药物与临床, 2019, 22:349-353.
[9]Gao T, Wu J, Zheng R, et al.Assessment of three essential tremor genetic loci in sporadic Parkinson's disease in Eastern China[J].CNS Drug Rev, 2020, 26:448-452.
[10]Zhang Y, Meng X, Jiao Z, et al.Generation of a novel mouse model of Parkinson's disease via targeted knock-down of glutamate transporter GLT-1 in the substantia nigra[J].ACS Chem Neurosci, 2020, 11:406-417.
[11]Aoyama K. Glutathione in the brain[J]. Int J Mol Sci, 2021, 22:5010-5014.
[12]Lee M, Dong GK, Hong DK, et al.Role of excitatory amino acid carrier 1 (EAAC1) in neuronal death and neurogenesis after ischemic stroke[J].Int J Mol Sci, 2020, 21:5676-5691.
[13]Piccirillo S, Magi S, Preziuso A, et al.Gateways for glutamate neuroprotection in Parkinson's disease (PD): essential role of EAAT3 and NCX1 revealed in an in vitro model of PD[J].Cells, 2020, 9:2037-2058.
[14]Takayasu Y.Differential roles of glial and neuronal glutamate transporters in purkinje cell synapses[J].J Neurosci, 2005, 25:8788-8793.
[15]Zhou L, Yang L, Li YJ, et al.MicroRNA-128 protects dopamine neurons from apoptosis and upregulates the expression of excitatory amino acid transporter 4 in Parkinson's disease by binding to AXIN1[J].Cell Physiol Biochem, 2018, 51:2275-2289.
[16]Buck SA, Steinkellner T, Aslanoglou D, et al.Vesicular glutamate transporter modulates sex differences in dopamine neuron vulnerability to age-related neurodegeneration[J].Aging Cell, 2021, 20:e13365-e13367.
[17]Rosin DL, Hettinger BD, Lee A, et al.Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function[J].Neurology, 2003, 61:S12-S18.
[18]Zheng X, Huang Z, Zhu Y, et al.Increase in gluta-matergic terminals in the striatum following dopamine depletion in a rat model of Parkinson's disease[J].Neurochem Res, 2019, 44:1079-1089.
[19]Shen H, Marino R, Mcdevitt RA, et al.Genetic deletion of vesicular glutamate transporter in dopamine neurons increases vulnerability to MPTP-induced neurotoxicity in mice[J]. Proc Natl Acad Sci U S A, 2018, 115:E11532-E11541.
[20]Steinkellner T, Zell V, Farino ZJ, et al.Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons[J]. J Clin Invest, 2018, 128:774-788.
[21]Gangarossa G, Guzman M, Prado VF, et al.Role of the atypical vesicular glutamate transporter VGLUT3 in l-DOPA-induced dyskinesia[J].Neurobiol Dis, 2016, 87:69-79.
[22]Favier M, Pietrancosta N, Mestikawy SE, et al.Leverag-ing VGLUT3 functions to untangle brain dysfunctions[J].Trends Pharmacol Sci, 2021, 42:475-490.