Axon self destruction: new links among SARM1, MAPKs, and NAD+ metabolism

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.