神经退行性疾病（NDs）以失控的神经细胞丧失为特征，导致大脑功能逐渐恶化。过去二十年中，无数神经保护药物对阿尔茨海默病、帕金森病、肌萎缩性脊髓侧索硬化症和亨廷顿病的过渡率，获得FDA批准仅为8-14%。因此，尽管有鼓舞人心的临床前结果，这些药物在人体临床试验中均失败，表明传统的细胞培养和动物模型无法准确复制人类病理生理学。因此，三维（3D）体外模型已经发展起来，以弥合人类和动物研究之间的差距。包括人工诱导多能干细胞（iPSC）衍生的细胞/器官样体、芯片器官技术和3D生物打印等在内的3D培养系统的技术进步，有助于我们了解人类NDs的病理生理学和潜在机制。尽管取得了这些近期的进展，我们仍然缺乏一个可以复制NDs所有关键方面的3D模型，这使得对该疾病的病因研究变得困难。因此，在本综述中，我们提议采用组合方法，允许患者衍生的iPSC/器官样体与3D生物打印和芯片器官技术的结合，以包含神经细胞及其周围环境。这种3D组合方法将彻底描述病理过程，使其更适用于高通量药物筛选和开发针对NDs的有效新型治疗。© 2023. 作者，独家授权给德国斯普林格维尔亚格有限公司，属于斯普林格自然的一部分。

Neurodegenerative diseases (NDs) are characterized by uncontrolled loss of neuronal cells leading to a progressive deterioration of brain functions. The transition rate of numerous neuroprotective drugs against Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, leading to FDA approval, is only 8-14% in the last two decades. Thus, in spite of encouraging preclinical results, these drugs have failed in human clinical trials, demonstrating that traditional cell cultures and animal models cannot accurately replicate human pathophysiology. Hence, in vitro three-dimensional (3D) models have been developed to bridge the gap between human and animal studies. Such technological advancements in 3D culture systems, such as human-induced pluripotent stem cell (iPSC)-derived cells/organoids, organ-on-a-chip technique, and 3D bioprinting, have aided our understanding of the pathophysiology and underlying mechanisms of human NDs. Despite these recent advances, we still lack a 3D model that recapitulates all the key aspects of NDs, thus making it difficult to study the ND's etiology in-depth. Hence in this review, we propose developing a combinatorial approach that allows the integration of patient-derived iPSCs/organoids with 3D bioprinting and organ-on-a-chip technique as it would encompass the neuronal cells along with their niche. Such a 3D combinatorial approach would characterize pathological processes thoroughly, making them better suited for high-throughput drug screening and developing effective novel therapeutics targeting NDs.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.