Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Prog Brain Res. 2020;252:3-25. doi: 10.1016/bs.pbr.2019.11.002. Epub 2019 Dec 10.
Parkinson's disease (PD) is an age-related neurodegenerative disorder with no known cure. In order to better understand the pathological mechanisms which lead to neuronal cell death and to accelerate the process of drug discovery, a reliable in vitro model is required. Unfortunately, research into PD and neurodegeneration in general has long suffered from a lack of adequate in vitro models, mainly due to the inaccessibility of live neurons from vulnerable areas of the human brain. Recent reprogramming technologies have recently made it possible to reliably derive human induced pluripotent stem cells (iPSCs) from patients and healthy subjects to generate specific, difficult to obtain, cellular sub-types. These iPSC-derived cells can be employed to model disease to better understand pathological mechanisms and underlying cellular vulnerability. Therefore, in this chapter, we will discuss the techniques involved in the reprogramming of somatic cells into iPSCs, the evolution of iPSC differentiation methods and their application in neurodegenerative disease modeling.
帕金森病（PD）是一种与年龄相关的神经退行性疾病，目前尚无已知的治愈方法。为了更好地了解导致神经元细胞死亡的病理机制，并加速药物发现的过程，需要一种可靠的体外模型。不幸的是，帕金森病和神经退行性疾病的研究长期以来一直受到缺乏足够的体外模型的困扰，主要是因为难以获得来自人类大脑脆弱区域的活神经元。最近的重编程技术最近使得从患者和健康受试者中可靠地衍生人类诱导多能干细胞（iPSC）成为可能，从而生成特定的、难以获得的细胞亚型。这些 iPSC 衍生的细胞可用于模拟疾病，以更好地了解病理机制和潜在的细胞脆弱性。因此，在本章中，我们将讨论体细胞重编程为 iPSC 的相关技术、iPSC 分化方法的演变及其在神经退行性疾病建模中的应用。
