Department of Neurology, Fukuoka University, Fukuoka 814-0180, Japan.
Int J Mol Sci. 2018 Dec 4;19(12):3870. doi: 10.3390/ijms19123870.
Parkinson's disease (PD) and atypical parkinsonian syndromes are age-dependent multifactorial neurodegenerative diseases, which are clinically characterized by bradykinesia, tremor, muscle rigidity and postural instability. Although these diseases share several common clinical phenotypes, their pathophysiological aspects vary among the disease categories. Extensive animal-based approaches, as well as postmortem studies, have provided important insights into the disease mechanisms and potential therapeutic targets. However, the exact pathological mechanisms triggering such diseases still remain elusive. Furthermore, the effects of drugs observed in animal models are not always reproduced in human clinical trials. By using induced pluripotent stem cell (iPSC) technology, it has become possible to establish patient-specific iPSCs from their somatic cells and to effectively differentiate these iPSCs into different types of neurons, reproducing some key aspects of the disease phenotypes in vitro. In this review, we summarize recent findings from iPSC-based modeling of PD and several atypical parkinsonian syndromes including multiple system atrophy, frontotemporal dementia and parkinsonism linked to chromosome 17 and Perry syndrome. Furthermore, we discuss future challenges and prospects for modeling and understanding PD and atypical parkinsonian syndromes.
帕金森病（PD）和非典型帕金森综合征是年龄依赖性的多因素神经退行性疾病，其临床特征为运动迟缓、震颤、肌肉僵硬和姿势不稳。尽管这些疾病具有一些共同的临床表型，但在疾病类别中，其病理生理方面存在差异。广泛的基于动物的方法以及尸检研究为疾病机制和潜在的治疗靶点提供了重要的见解。然而，引发这些疾病的确切病理机制仍难以捉摸。此外，在动物模型中观察到的药物作用并不总是在人类临床试验中重现。通过使用诱导多能干细胞（iPSC）技术，已经可以从其体细胞中建立患者特异性的 iPSC，并有效地将这些 iPSC 分化为不同类型的神经元，在体外重现疾病表型的一些关键方面。在这篇综述中，我们总结了基于 iPSC 的 PD 和几种非典型帕金森综合征（包括多系统萎缩、额颞叶痴呆和与 17 号染色体相关的帕金森病以及佩里综合征）建模的最新发现。此外，我们讨论了建模和理解 PD 和非典型帕金森综合征的未来挑战和前景。
