Modeling Parkinson's Disease Using Patient-specific Induced Pluripotent Stem Cells.
Modeling Parkinson's Disease Using Patient-specific Induced Pluripotent Stem Cells.
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DOI：
10.3233/jpd-181353
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Feng J
中科院分区：
文献类型：
--
作者：
Li H;Jiang H;Zhang B;Feng J
帕金森病（PD）是第二常见的神经退行性疾病。其特征在于黑质多巴胺能（DA）神经元的变性。虽然超过90%的病例是特发性的，但没有明确的病因，许多基因的突变与罕见的家族性PD有关。开发有效的PD动物模型以捕捉PD的显著特征一直是相当具有挑战性的。诱导多能干细胞（iPSC）的发现使得产生患者特异性DA神经元以研究PD成为可能。在这里，我们回顾了产生iPSC的方法，并讨论了以前的研究使用iPSC衍生的神经元从单基因形式的PD。这些研究揭示了几个与人类黑质DA神经元独特脆弱性交叉的会聚途径。随着干细胞生物学的快速发展，有可能产生与患者大脑中的神经元越来越相似的患者特异性神经元。结合编辑基因组以产生等基因iPSC的能力，患者特异性中脑DA神经元的产生和分析将通过为机制研究和药物发现提供有价值的工具来改变PD研究。
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by the degeneration of nigral dopaminergic (DA) neurons. While over 90% of cases are idiopathic, without a clear etiology, mutations in many genes have been linked to rare, familial forms of PD. It has been quite challenging to develop effective animal models of PD that capture salient features of PD. The discovery of induced pluripotent stem cells (iPSCs) makes it possible to generate patient-specific DA neurons to study PD. Here, we review the methods for the generation of iPSCs and discuss previous studies using iPSC-derived neurons from monogenic forms of PD. These investigations have revealed several converging pathways that intersect with the unique vulnerabilities of human nigral DA neurons. With the rapid development in stem cell biology, it is possible to generate patient-specific neurons that will be increasingly similar to those in the brain of the patient. Combined with the ability to edit the genome to generate isogenic iPSCs, the generation and analysis of patient-specific midbrain DA neurons will transform PD research by providing a valuable tool for mechanistic study and drug discovery.