Sterile-α and TIR motif-containing protein 1 (SARM1) is an essential mediator of axon degeneration, and increased levels of NAD+ are neuroprotective, but the link between the two remains unclear. A recent paper showed that, in mice, dimerization of the Toll–interleukin receptor (TIR) domain of SARM1 induced rapid breakdown of NAD+ and was sufficient to induce axon degeneration; this effect was reversed by increased synthesis of NAD+, suggesting that NAD+ loss is a key step in SARM1-mediated axon degeneration.
References
Gerdts, J. et al. SARM1 activation triggers axon degeneration locally via NAD+ destruction. Science 348, 453–457 (2015)
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Lewis, S. Neurodegeneration takes its TOLL. Nat Rev Neurosci 16, 316 (2015). https://doi.org/10.1038/nrn3971
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DOI: https://doi.org/10.1038/nrn3971
