National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Drug Discov Today. 2019 Apr;24(4):992-999. doi: 10.1016/j.drudis.2019.01.007. Epub 2019 Jan 18.
Neurological diseases such as Alzheimer's disease and Parkinson's disease are growing problems, as average life expectancy is increasing globally. Drug discovery for neurological disease remains a major challenge. Poor understanding of disease pathophysiology and incomplete representation of human disease in animal models hinder therapeutic drug development. Recent advances with induced pluripotent stem cells (iPSCs) have enabled modeling of human diseases with patient-derived neural cells. Utilizing iPSC-derived neurons advances compound screening and evaluation of drug efficacy. These cells have the genetic backgrounds of patients that more precisely model disease-specific pathophysiology and phenotypes. Neural cells derived from iPSCs can be produced in a large quantity. Therefore, application of iPSC-derived human neurons is a new direction for neuronal drug discovery.
神经退行性疾病(如阿尔茨海默病和帕金森病)是一个日益严重的问题,因为全球的平均预期寿命正在增加。神经退行性疾病的药物发现仍然是一个主要挑战。对疾病病理生理学的理解不足,以及动物模型中对人类疾病的不完全代表性,阻碍了治疗药物的开发。诱导多能干细胞(iPSC)的最新进展使得能够利用患者来源的神经细胞对人类疾病进行建模。利用 iPSC 衍生的神经元可促进化合物筛选和药物疗效评估。这些细胞具有患者的遗传背景,更能精确地模拟特定疾病的病理生理学和表型。iPSC 衍生的神经元可以大量产生。因此,应用 iPSC 衍生的人类神经元是神经药物发现的一个新方向。