Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism

• Published in: Neuron (Cambridge, Mass.) Vol. 89; no. 3; pp. 449 - 460
• Main Authors: Gerdts, Josiah, Summers, Daniel W., Milbrandt, Jeffrey, DiAntonio, Aaron
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.02.2016; Elsevier Limited
• Subjects: Alzheimer's disease; Animals; Apoptosis; Armadillo Domain Proteins - metabolism; Axons - metabolism; Axons - pathology; Cytoskeletal Proteins - metabolism; Cytoskeleton; Humans; Kinases; Metabolism; Mitogen-Activated Protein Kinases - metabolism; NAD - metabolism; Neurodegeneration; Neuroprotective Agents - metabolism; Nicotinamide-Nucleotide Adenylyltransferase - metabolism; Rodents; Signal Transduction; Wallerian Degeneration - metabolism; Wallerian Degeneration - pathology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.12.023

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. Injury-induced axonal degeneration is an active program of subcellular self-destruction that promotes axon breakdown during injury and disease. Gerdts et al. discuss the roles for SARM1, MAPK signaling, and NAD+ metabolism in a unified model of the axon degeneration program.