Molecular mechanisms underlying Wallerian degeneration of axons have been elucidated in the past 30 years, demonstrating that NAD+ synthesizing enzyme NMNAT2 and NAD+ hydrolase Sarm1, play critical roles in the process. In the past 7 years, we also know that distal slow axon degeneration seen in peripheral neuropathies and neurodegenerative diseases share the same mechanisms because genetic deletion of Sarm1 is a potent preventor of distal axon degeneration in animal models. Furthermore, pharmacological and genetic inhibitors of Sarm1 activity are likely potent therapeutic options for several common neurological diseases, including chemotherapy-induced peripheral neuropathy and diabetic neuropathy.
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Dr. Hoke also serves as Editor-in-Chief, Annals of Clinical and Translational Neurology Johns Hopkins School of Medicine.