Jacobs Benjamin Meir
Magdalen College, Oxford University, Oxford, UK.
J Parkinsons Dis. 2014;4(1):15-27. doi: 10.3233/JPD-130268.
Parkinson's disease (PD) is a prevalent and debilitating neurodegenerative disorder for which there are no available cures. PD pathogenesis is poorly understood because appropriate animal and in vitro models are lacking. The development of induced Pluripotent Stem Cells (iPSCs) has allowed researchers to generate disease-specific dopaminergic neurons in vitro by reprogramming skin cells from patients with the disease. It is hoped that this unprecedented access to PD patients' neurons will yield mechanistic insights into PD pathogenesis, a platform for drug screening, and a means of early diagnosis. In this article I critically evaluate the current usage of iPSCs in PD research. I first outline the iPSC paradigm and emphasise the benefits of this approach for modelling PD. I then ask what we can learn from the iPSC-based studies done to date. I argue that these studies have not been particularly informative when considered as an isolated body of evidence. I suggest that the limitations of this technology can be overcome, and I conclude that iPSCs have the potential to be an extremely useful tool in PD research. However, they will never be a panacea and should continue to be used in concert with other in vitro and animal models.
帕金森病(PD)是一种常见且使人衰弱的神经退行性疾病,目前尚无治愈方法。由于缺乏合适的动物模型和体外模型,PD的发病机制尚不清楚。诱导多能干细胞(iPSC)的发展使研究人员能够通过重编程患病患者的皮肤细胞,在体外生成疾病特异性的多巴胺能神经元。人们希望,这种前所未有的获取PD患者神经元的方式,将为PD发病机制提供机制性见解、一个药物筛选平台以及一种早期诊断手段。在本文中,我批判性地评估了iPSC在PD研究中的当前应用。我首先概述了iPSC范式,并强调了这种方法在模拟PD方面的优势。然后我探讨了我们能从迄今为止基于iPSC的研究中学到什么。我认为,当将这些研究视为一个孤立的证据体系时,它们并没有特别丰富的信息。我建议可以克服这项技术的局限性,并得出结论,iPSC有潜力成为PD研究中极其有用的工具。然而,它们永远不会是万灵药,应该继续与其他体外和动物模型一起使用。