Monitoring Axonal Degeneration in Human Pluripotent Stem Cell Models of Hereditary Spastic Paraplegias.
Monitoring Axonal Degeneration in Human Pluripotent Stem Cell Models of Hereditary Spastic Paraplegias.
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DOI：
10.1007/7651_2021_379
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
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作者：
Li XJ;Mou Y;Milton C;Chen Z
轴突变性是许多衰弱性疾病的基础，包括遗传性痉挛性截瘫（HSP）。热休克蛋白是一个大的异质性组的神经退行性疾病，其特征在于轴突病变涉及长皮质脊髓束。这些皮质投射神经元的轴突如何特异性地在热休克蛋白中变性仍然很不清楚，部分原因是缺乏人类模型来监测轴突变性的动态过程。随着诱导性多能干细胞（iPSC）技术的发展，从HSP患者成功地产生了患者特异性iPSC，为在活培养物中研究患者源性神经元的轴突变性提供了独特的范例。在本章中，我们将总结检查HSP的iPSC模型中的轴突缺陷的程序，并讨论挑战和未来的应用，以挽救HSP中的轴突变性。
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.