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Cell Death and Dis:适用于研究帕金森病神经退行性变的新模型

2019-12-10 QQY MedSci原创

帕金森病的一个主要特征是黑质致密带(SNpc)多巴胺能神经元的丧失。但这种相对选择性的神经退行性变的病理生理机制尚不明确,因此需要研究多巴胺能神经元功能障碍的实验系统。而诱导多能干细胞(iPSC)向多巴胺能神经元分化的实验也为获得人源性的多巴胺能神经元提供了宝贵的来源。但就目前可用的实验方案而言,将人源hiPSC诱导成多巴胺能神经元的产量也有所不同。在本研究中,研究人员开发了一种基于HBA启动子驱

帕金森病的一个主要特征是黑质致密带(SNpc)多巴胺能神经元的丧失。但这种相对选择性的神经退行性变的病理生理机制尚不明确,因此需要研究多巴胺能神经元功能障碍的实验系统。而诱导多能干细胞(iPSC)向多巴胺能神经元分化的实验也为获得人源性的多巴胺能神经元提供了宝贵的来源。

但就目前可用的实验方案而言,将人源hiPSC诱导成多巴胺能神经元的产量也有所不同。在本研究中,研究人员开发了一种基于HBA启动子驱动的转录因子瞬时表达的方案,通过腺相关病毒(AAV)载体,能够从四种不同的人iPSC系获得数量一样的多巴胺能神经元。

研究人员还证明了AAV载体表达的来自神经元特异性hSyn1启动子的报告基因可用来充当hiPSC诱导分化的多巴胺能神经元成熟的标记。

通过转录因子表达诱导分化的多巴胺能神经元,在α-突触核蛋白(α-synuclein)过表达时,可发生神经变性加剧,但对γ-突触核蛋白(γ-synuclein)过表达不敏感,该结果提示这些诱导分化出的神经元非常适合研究帕金森病背景下的神经变性。

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    2020-04-16 维他命
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    2019-12-12 cy0328
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    2019-12-10 CHANGE

    梅斯里提供了很多疾病的模型计算公式,赞一个!

    0

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帕金森病是一类常见的神经退行性疾病。在这些患者的神经细胞里,往往能看到一类叫做路易小体(Lewy bodies)的结构,里头是α突触核蛋白的积聚。如何针对这类蛋白,避免路易小体的产生,也是帕金森病治疗领域的一个热门方向。

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