Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, BSB 409, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Curr Neurol Neurosci Rep. 2018 Oct 4;18(12):84. doi: 10.1007/s11910-018-0893-8.
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting older individuals. The specific cause underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the potential disease-relevant phenotypes that may lead to a better understanding of PD etiology. Benefits of iPSCs are that they retain the genetic background of the donor individual and can be differentiated into specialized neurons to facilitate disease modeling.
Mitochondrial dysfunction, oxidative stress, ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD iPSC-derived neurons. New culturing technologies, such as directed reprogramming and midbrain organoids, offer innovative ways of investigating intraneuronal mechanisms of PD pathology. PD patient-derived iPSCs are an evolving resource to understand PD pathology and identify therapeutic targets.
综述目的：帕金森病（PD）是影响老年人的第二大常见神经退行性疾病。导致黑质多巴胺（DA）神经元丧失的具体原因仍然难以捉摸，这是 PD 的一个病理标志。在这里，我们重点介绍了使用诱导多能干细胞（iPSCs）在体外模拟 PD 的同行评审报告，并讨论了可能导致更好地了解 PD 病因的潜在与疾病相关的表型。iPSCs 的优点是它们保留了供体个体的遗传背景，并可分化为专门的神经元，以促进疾病建模。
最新发现：在 PD iPSC 衍生神经元中观察到线粒体功能障碍、氧化应激、内质网应激和α-突触核蛋白积累等常见表型。定向重编程和中脑神经器官等新的培养技术为研究 PD 病理学的神经元内机制提供了创新方法。PD 患者来源的 iPSCs 是理解 PD 病理学和确定治疗靶点的不断发展的资源。
