Department of Pharmaceutical Sciences, JH School of Pharmacy, Texas Tech University Health Sciences Center (TTUHSC), Amarillo, TX 79106, USA.
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Drug Discov Today. 2020 Feb;25(2):456-465. doi: 10.1016/j.drudis.2019.11.010. Epub 2019 Nov 26.
The paradigm of central nervous system (CNS) drug discovery has mostly relied on traditional approaches of rodent models or cell-based in vitro models. Owing to the issues of species differences between humans and rodents, it is difficult to correlate the robustness of data for neurodevelopmental studies. With advances in the stem-cell field, 3D CNS organoids have been developed and explored owing to their resemblance to the human brain architecture and functions. Further, CNS organoids provide a unique opportunity to mimic the human brain physiology and serve as a modeling tool to study the normal versus pathological brain or the elucidation of mechanisms of neurological disorders. Here, we discuss the recent application of a CNS organoid explored for neurodevelopment disease or a screening tool for CNS drug development.
中枢神经系统(CNS)药物发现的范例主要依赖于啮齿动物模型或基于细胞的体外模型的传统方法。由于人类和啮齿动物之间存在物种差异的问题,因此很难将神经发育研究的数据的稳健性进行关联。随着干细胞领域的进步,已经开发和探索了 3D CNS 类器官,因为它们与人脑的结构和功能相似。此外,CNS 类器官为模拟人脑生理学提供了独特的机会,并作为研究正常与病理性大脑或阐明神经疾病机制的建模工具。在这里,我们讨论了最近对 CNS 类器官的应用,该应用探索了神经发育疾病或 CNS 药物开发的筛选工具。