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Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism
Josiah Gerdts1, Daniel W Summers2, Jeffrey Milbrandt3
1Department of Genetics, Washington University School of Medicine in St. Louis, 660 Euclid Avenue, St. Louis, MO 63110, USA.
Abstract:
Wallerian axon degeneration is a form of programmed subcellular death that promotes axon breakdown in disease and injury. Active degeneration requires SARM1 and MAP kinases, including DLK, while the NAD+ synthetic enzyme NMNAT2 prevents degeneration. New studies reveal that these pathways cooperate in a locally mediated axon destruction program, with NAD+ metabolism playing a central role. Here, we review the biology of Wallerian-type axon degeneration and discuss the most recent findings, with special emphasis on critical signaling events and their potential as therapeutic targets for axonopathy.
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