帕金森病个体化治疗靶点之一:hvWAT2

hVMAT2: A Target of Individualized Medication for Parkinson’s Disease
2016-06-14 09:01发表评论
作者:Xiong N, Li N, Martin E, Yu J, Li J, Liu J6, Lee DY, Isacson, Vance J, Qing H, Wang T, Lin Z.
机构: 中国湖北武汉,华中科技大学同济医学院附属协和医院神经内科
期刊: Neurotherapeutics2016年5月期卷

Vesicular monoamine transporter 2 (VMAT2) is responsible for sequestering cytosolically toxic dopamine into intracellular secretory vesicles. Animal genetic studies have suggested that reduced VMAT2 activity contributes to the genetic etiology of Parkinson’s disease (PD), but this role has not been established in humans. Based on human genetic association and meta-analysis, we first confirm the human VMAT2 (hVMAT2 or SLC18A2) promoter as a risk factor for PD in both family and unrelated US white people: marker rs363324 at –11.5 kb in the hVMAT2 promoter is reproducibly associated with PD in a cohort of nuclear families (p = 0.04506 in early-onset PD) and 3 unrelated US white people (meta-analysis p = 0.01879). In SH-SY5Y cells, low activity-associated hVMAT2 promoter confers high methylpiperidinopyrazole iodide cytotoxicity, which is likely attributed to functional polymorphisms bound by nuclear proteins. Interestingly, treatments with the dopamine neuron-protecting agent puerarin upregulates the promoter activity in a haplotype- and cell line-dependent manner. These pharmacogenetic findings suggest that hVMAT2 could be a risk factor and imply it as a target of genetic medications for PD. © 2016 The American Society for Experimental NeuroTherapeutics, Inc.

通讯机构:Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
学科代码:神经病学 神经外科学   关键词:帕金森病 个体化治疗靶点 ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
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