Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.
Bottom Line: Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury.We also present evidence that myelinophagy is defective in the injured central nervous system.These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.Show MeSH
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Mentions: Ceramide has been proposed to act via the JNK/c-Jun pathway to promote autophagy (Ravikumar et al., 2010). We reported previously that c-Jun is a master regulator of the Schwann cell response to injury, and that myelin protein and lipid degradation are delayed in c-Jun cKO mice (Arthur-Farraj et al., 2012). Accordingly, treatment with JNK inhibitor SP600125 strongly inhibited myelin protein breakdown in Schwann cell cultures (Fig. 6, B and C). To test whether the JNK/c-Jun pathway regulated myelinophagy, we examined autophagic flux in nerves from WT mice treated with SP600125 and nerves from WT and c-Jun cKO mice. Autophagic flux was significantly reduced in SP600125-treated and c-Jun cKO nerves (Fig. 7, A and B). This indicates that the JNK/c-Jun pathway is involved in driving Schwann cell autophagy in injured nerves.
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.