Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
J Parkinsons Dis. 2019;9(2):265-281. doi: 10.3233/JPD-181515.
Studying Parkinson's disease (PD) in the laboratory presents many challenges, the main one being the limited availability of human cells and tissue from affected individuals. As PD is characterized by a loss of dopaminergic (DA) neurons in the brain, it is nearly impossible for researchers to access and extract these cells from living patients. Thus, in the past PD research has focused on the use of patients' post-mortem tissues, animal models, or immortalized cell lines to dissect cellular pathways of interest. While these strategies deepened our knowledge of pathological mechanisms in PD, they failed to faithfully capture key mechanisms at play in the human brain. The emergence of induced pluripotent stem cell (iPSC) technology is revolutionizing PD research, as it allows for the differentiation and growth of human DA neurons in vitro, holding immense potential not only for modelling PD, but also for identifying novel therapies. However, to reproduce the complexity of the brain's environment, researchers are recognizing the need to further develop and refine iPSC-based tools. In this review, we provide an overview of different systems now available for the study of PD, with a particular emphasis on the potential and limitations of iPSC as research tools to generate more relevant models of PD pathophysiology and advance the drug discovery process.
研究帕金森病（PD）在实验室中存在许多挑战，主要的一个挑战是，从受影响的个体中获得的人类细胞和组织的有限可用性。由于 PD 的特征是大脑中的多巴胺能（DA）神经元丧失，研究人员几乎不可能从活着的患者中获取和提取这些细胞。因此，过去 PD 的研究主要集中在使用患者的死后组织、动物模型或永生化细胞系来剖析感兴趣的细胞途径上。虽然这些策略加深了我们对 PD 病理机制的了解，但它们未能真实地捕捉到在人类大脑中起作用的关键机制。诱导多能干细胞（iPSC）技术的出现正在彻底改变 PD 的研究，因为它允许在体外分化和生长人类 DA 神经元，不仅在 PD 建模方面具有巨大的潜力，而且在鉴定新的治疗方法方面也具有巨大的潜力。然而，为了重现大脑环境的复杂性，研究人员认识到需要进一步开发和改进基于 iPSC 的工具。在这篇综述中，我们提供了 PD 研究中现有不同系统的概述，特别强调了 iPSC 作为研究工具的潜力和局限性，以生成更相关的 PD 病理生理学模型，并推进药物发现过程。
