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.
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Acknowledgments
We thank Drs. Tatsuya Osaki, Jiro Kawada, and Teruo Fujii for critical discussion and insightful inputs on the manuscript. We also thank all members of Ikeuchi lab and Fujii lab for comments and discussion. This work was supported in part by WINGS-LST (A.C.), the Japan Society for the Promotion of Science (JSPS) with a Grant-in-Aid for a Challenging Research (Pioneering) (20 K20643), the Grant-in-Aid for Transformative Research Areas (B) (20H05786), AMED-CREST, AMED (JP20gm1410001), and Institute for AI and Beyond (Y.I.). The test of edaravone was performed in collaboration with Tanabe Mitsubishi Pharma Company.
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Chow, S.Y.A., Nakanishi, Y., Kaneda, S., Ikeuchi, Y. (2022). Modeling Axonal Degeneration Using Motor Nerve Organoids. In: Jahani-Asl, A. (eds) Neuronal Cell Death. Methods in Molecular Biology, vol 2515. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2409-8_6
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DOI: https://doi.org/10.1007/978-1-0716-2409-8_6
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Publisher Name: Humana, New York, NY
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