Activation of the NAD hydrolase domain of Sarm1 mediates axonal degeneration caused by chemotherapy drugs, but the downstream events are unknown. In this issue, Li and colleagues (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202106080) demonstrate that cADPR, a breakdown product of NAD, mediates paclitaxel-induced axonal degeneration by promoting influx of calcium into the axons.
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