Despite their large societal burden, the development of therapeutic treatments for neurodegenerative diseases (NDDs) has been relatively unsuccessful. This is, in part, due to a lack of representative experimental models that reveal fundamental aspects of human brain pathology. Recently, assays for in vitro modeling of the human central nervous system (CNS) have significantly improved with the development of brain and spinal cord organoids. Coupled with induced-pluripotent stem cell and genome editing technologies, CNS organoids are a promising tool for studying neurodegeneration in a patient-specific manner. An extensive array of protocols for the generation of organoids for different brain regions has been developed and used for studying neurodegenerative and other brain diseases. However, their application in the field of motor neuron disease (MND) has been limited due to a lack of adequate organoid models. The development of protocols to derive spinal cord and trunk organoids and progress in the field of assembloids are providing new opportunities for modeling MND. In this study here we review recent advances in the development of CNS organoid models, their application in NDDs, and technical limitations. Finally, we discuss future perspectives for the development of organoid-based systems for MND and provide a framework for their development.

中文翻译：

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中枢神经系统类器官的进展：关注基于类器官的运动神经元疾病模型

尽管他们的社会负担很大，但神经退行性疾病 (NDD) 治疗方法的开发相对不成功。这部分是由于缺乏揭示人类大脑病理学基本方面的代表性实验模型。最近，体外检测随着大脑和脊髓类器官的发育，人类中枢神经系统 (CNS) 的建模得到了显着改善。结合诱导多能干细胞和基因组编辑技术，中枢神经系统类器官是一种以患者特异性方式研究神经变性的有前途的工具。已经开发了大量用于为不同大脑区域生成类器官的协议，并用于研究神经退行性疾病和其他大脑疾病。然而，由于缺乏足够的类器官模型，它们在运动神经元疾病 (MND) 领域的应用受到限制。衍生脊髓和躯干类器官的协议的发展以及组合体领域的进展为 MND 建模提供了新的机会。在这里的这项研究中，我们回顾了 CNS 类器官模型开发的最新进展、它们在 NDD 中的应用以及技术限制。最后，我们讨论了开发基于类器官的 MND 系统的未来前景，并为其开发提供了一个框架。