Li Qing-Jun, Tang Ya-Mei, Liu Jun, Zhou Dao-You, Li Xiang-Pen, Xiao Song-Hua, Jian Dong-Xing, Xing Yi-Gang
Department of Neurology, Dong Guan People Hospital, Dong Guan 523018, China.
Synapse. 2007 Dec;61(12):971-7. doi: 10.1002/syn.20449.
To study the potential benefit of the NURR1 gene in Parkinson's disease (PD), we constructed a recombinant republic-deficit adenovirus containing the NURR1 gene (Ad-NURR1) and expressed it in transplanted neural stem cells (NSC). Ad-NURR1 was constructed, and NURR1 mRNA and protein expression were identified by in situ hybridization and western blot analysis, respectively. The identified NURR1 protein could directly or indirectly induce NSC differentiation into neurons. To identify a potential therapeutic use for the transfected NSCs, cells were transplanted into 6-hydroxydopamine lesioned rats. Histopathological and behavioral alterations were evaluated via immunohistochemistry and the ration test, respectively, in rats transplanted with NSCs with or without the Ad-NURR1 adenovirus. The Ad-NURR1 construct effectively expressed the NURR1 protein, which could directly or indirectly induce NSC differentiation into neurons. Both histopathological and behavioral alterations were seen in rats treated with NSCs with or without the Ad-NURR1 construct, although in the case of the latter, the benefits were more robust. These results suggest a potential therapeutic benefit for Ad-NURR1-expressing cells in the treatment of PD. The Ad-NURR1 modification induced NSC differentiation and therefore represents a potential therapy for PD.
为研究NURR1基因在帕金森病（PD）中的潜在益处，我们构建了一种携带NURR1基因的重组缺损型腺病毒（Ad-NURR1），并使其在移植的神经干细胞（NSC）中表达。构建了Ad-NURR1，并分别通过原位杂交和蛋白质印迹分析鉴定了NURR1 mRNA和蛋白质表达。鉴定出的NURR1蛋白可直接或间接诱导NSC分化为神经元。为确定转染的NSC的潜在治疗用途，将细胞移植到6-羟基多巴胺损伤的大鼠体内。分别通过免疫组织化学和定量试验评估了移植有含或不含Ad-NURR1腺病毒的NSC的大鼠的组织病理学和行为改变。Ad-NURR1构建体有效表达了NURR1蛋白，该蛋白可直接或间接诱导NSC分化为神经元。在接受含或不含Ad-NURR1构建体的NSC治疗的大鼠中均观察到了组织病理学和行为改变，尽管在后一种情况下，益处更为显著。这些结果表明表达Ad-NURR1的细胞在治疗PD方面具有潜在的治疗益处。Ad-NURR1修饰诱导了NSC分化，因此代表了一种治疗PD的潜在疗法。
