Axonal injuries can trigger a process of axonal disintegration known as Wallerian degeneration, which is thought to be largely driven by intrinsic mechanisms in the axon. Here, knocking out the death receptor 6 (Dr6) gene in cultured mouse sympathetic or dorsal root ganglion neurons was associated with prolonged preservation of axons in an intact state following axotomy. Moreover, following sciatic nerve axotomy, mice lacking Dr6 exhibited marked preservation of axons in sciatic nerves compared with wild-type mice. Finally, the absence of DR6 was associated with a lack of activation of a kinase implicated in Wallerian degeneration. This study indicates that a neuronal receptor has a key role in this process.
Gamage, K. K. et al. Death receptor 6 promotes Wallerian degeneration in peripheral axons. Curr. Biol. 27, 890–896 (2017)
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Yates, D. A receptor for injury. Nat Rev Neurosci 18, 266 (2017). https://doi.org/10.1038/nrn.2017.50