StemBANCC, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Molecular Neurodegeneration Group, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Neuropharmacology. 2014 Jan;76 Pt A:88-96. doi: 10.1016/j.neuropharm.2013.08.035. Epub 2013 Sep 10.
Parkinson's disease (PD) is the second most common neurodegenerative disease, with a strong genetic component to both the familial and sporadic forms. The cardinal motor symptoms of the disease result from the loss of dopamine (DA) neurons in the midbrain. There is currently no cure for PD and improved methods for modelling the disease are required in order to develop more effective therapeutic interventions. Patient-derived induced pluripotent stem cells (iPSCs) carry the genetic background of the donor, enabling accurate modelling of genetic diseases in vitro. Various human iPSCs from patients suffering different genetic forms of PD have been differentiated into DA neurons and demonstrated signs of the pathophysiology of PD in vitro. The examination of key cellular pathways such as calcium regulation and autophagy indicate that disease-associated genetic variants may have important implications for cellular function. This review examines and critiques how DA neurons from patient iPSCs have been used to model PD in vitro, and what iPSCs might hold for the future of PD research. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.
帕金森病（PD）是第二常见的神经退行性疾病，无论是家族性还是散发性形式，都有很强的遗传成分。该疾病的主要运动症状是由于中脑多巴胺（DA）神经元的丧失引起的。目前尚无治愈 PD 的方法，需要改进疾病建模方法，以便开发更有效的治疗干预措施。供体携带遗传背景的患者来源诱导多能干细胞（iPSCs），能够在体外对遗传疾病进行精确建模。已经将来自患有不同遗传形式 PD 的患者的各种人 iPSCs 分化为 DA 神经元，并在体外显示出 PD 病理生理学的迹象。对钙调节和自噬等关键细胞途径的检查表明，与疾病相关的遗传变异可能对细胞功能具有重要意义。这篇综述检查和评论了如何使用来自患者 iPSCs 的 DA 神经元在体外对 PD 进行建模，以及 iPSCs 可能对 PD 研究的未来有何影响。本文是题为“神经退行性疾病的突触基础”的特刊的一部分。
