Systemic loss of Sarm1 protects Schwann cells from chemotoxicity by delaying axon degeneration
Lopez-Schier, H.; Tian, W.; Czopka, T.
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The obligate pro-degenerative protein Sarm1 is essential for Wallerian axon degeneration. Inhibition of Sarm1 has been proposed as a promising neuroprotective strategy with clinical relevance. Yet, the conditions that will most benefit from inhibiting Sarm1 remain undefined. Here we use genetics and pharmacology in zebrafish to show that systemic elimination of Sarm1 is glioprotective. Loss of Sarm1 does not affect macrophage recruitment to the wound microenvironment, focal injury resolution, or nerve repair. Unexpectedly, Sarm1 deficiency increases Schwann-cell resistance to toxicity by diverse chemotherapeutic agents after neuronal injury. Yet, synthetic degradation of Sarm1-deficient severed axons reversed this effect, suggesting that glioprotection is non-cell-autonomous. These findings anticipate that interventions aimed at inhibiting Sarm1 can counter heightened glial vulnerability to chemical stressors and may be an effective strategy to reduce chronic consequences of neurotrauma.
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