Monitoring Axonal Degeneration in Human Pluripotent Stem Cell Models of Hereditary Spastic Paraplegias.

Abstract

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.