Neurodegenerative diseases are incurable and debilitating conditions characterized by the deterioration of brain function. Most brain disease models rely on human post‐mortem brain tissue, non‐human primate tissue, or in vitro two‐dimensional (2D) experiments. Resource limitations and the complexity of the human brain are some of the reasons that make suitable human neurodegenerative disease models inaccessible. However, recently developed three‐dimensional (3D) brain organoids derived from pluripotent stem cells (PSCs), including embryonic stem cells and induced PSCs, may provide suitable models for the study of the pathological features of neurodegenerative diseases. In this review, we provide an overview of existing 3D brain organoid models and discuss recent advances in organoid technology that have increased our understanding of brain development. Moreover, we explain how 3D organoid models recapitulate aspects of specific neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, and explore the utility of these models, for therapeutic applications.

中文翻译：

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使用 3D 大脑类器官模拟神经退行性疾病

神经退行性疾病是无法治愈且使人衰弱的疾病，其特征在于大脑功能的恶化。大多数脑部疾病模型依赖于人类死后脑组织、非人类灵长类动物组织或体外二维 (2D) 实验。资源限制和人脑的复杂性是导致无法获得合适的人类神经退行性疾病模型的一些原因。然而，最近开发的源自多能干细胞 (PSC) 的三维 (3D) 脑类器官，包括胚胎干细胞和诱导 PSC，可能为研究神经退行性疾病的病理特征提供合适的模型。在这次审查中，我们概述了现有的 3D 大脑类器官模型，并讨论了类器官技术的最新进展，这些进展增加了我们对大脑发育的理解。此外，我们解释了 3D 类器官模型如何概括特定神经退行性疾病的各个方面，包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化和亨廷顿病，并探索这些模型在治疗应用中的效用。