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使用运动神经类器官模型进行轴突变性研究。

Modeling Axonal Degeneration Using Motor Nerve Organoids.

机构信息

Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.

Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan.

出版信息

Methods Mol Biol. 2022;2515:89-97. doi: 10.1007/978-1-0716-2409-8_6.

Abstract

Degeneration of axons is characteristic of many devastating diseases including amyotrophic lateral sclerosis (ALS). However, lack of an in vitro neuronal culture system that mimics damages on nerves and axonal tracts hampered development of effective treatments. Here, we describe a method to model degeneration of motor neuron axons using motor nerve organoids that are formed with human induced pluripotent stem cells. In this protocol, motor neuron axon degeneration can be rapidly induced with chemical damages. Neuroprotective effects of compounds can be examined using the degenerated axons. This motor neuron axon bundle degeneration model should facilitate future screening for drugs against diseases affecting axon fascicles.

摘要

轴突退变是许多破坏性疾病的特征,包括肌萎缩侧索硬化症(ALS)。然而,缺乏模拟神经和轴突损伤的体外神经元培养系统,阻碍了有效治疗方法的发展。在这里,我们描述了一种使用人诱导多能干细胞形成的运动神经类器官来模拟运动神经元轴突退变的方法。在这个方案中,可以用化学损伤快速诱导运动神经元轴突退变。可以用退变的轴突来检测化合物的神经保护作用。这种运动神经元轴突束退变模型应该有助于未来筛选针对影响轴突束疾病的药物。

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