Department of Biomedical Sciences, University of Illinois College of Medicine Rockford, Rockford, IL, USA.
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
Methods Mol Biol. 2022;2549:69-83. doi: 10.1007/7651_2021_379.
Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegias (HSPs). HSPs are a large heterogeneous group of neurodegenerative diseases characterized by axonopathy involving the long corticospinal tract. How axons of these cortical projection neurons specifically degenerate in HSPs remains largely unclear partially due to the lack of human models to monitor the dynamic process of axonal degeneration. With the development of induced pluripotent stem cell (iPSC) technology, patient-specific iPSCs are successfully generated from HSP patients, providing a unique paradigm to study the axonal degeneration in patient-derived neurons in live cultures. In this chapter, we will summarize the procedures to examine axonal defects in iPSC models of HSPs and discuss the challenges and future applications in order to rescue axonal degeneration in HSPs.
轴突变性是许多使人虚弱的疾病的基础，包括遗传性痉挛性截瘫 (HSPs)。HSPs 是一组大型异质性神经退行性疾病，其特征是涉及长皮质脊髓束的轴突病。这些皮质投射神经元的轴突如何特异性地在 HSPs 中退化仍不清楚，部分原因是缺乏用于监测轴突退化的动态过程的人类模型。随着诱导多能干细胞 (iPSC) 技术的发展，成功地从 HSP 患者中产生了患者特异性 iPSC，为在活培养物中研究源自患者的神经元中的轴突退化提供了独特的范例。在本章中，我们将总结检查 HSPs 的 iPSC 模型中轴突缺陷的程序，并讨论克服挑战和未来的应用，以拯救 HSPs 中的轴突退化。
