Deciphering changes in intracellular signals during axon degeneration

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In this study, our specific aim is to decipher mechanisms and factors that regulate the process of axon degeneration, a hallmark phenotype observed in various neurological disorders including Alzheimer’s disease. We developed aglutamate excitotoxicity-induced axon degeneration system in primary neuronal culturesand found that p150Glued and dynein intermediate chain (DIC), both of which are major components of the retrograde transport dynein-dynactin complex, microtubule stabilization, and inhibition of p53 transactivation regulate the process of axondegeneration including axon degeneration. As glutamate excitotoxicity is implicated in various neurological deficits, our findings identify retrograde transport proteins,microtubule dynamics, and tumor suppressor protein p53 as novel intracellular signalingmodulators of axon degeneration observed in neurological disorders.