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
Related in: MedlinePlus
License 1 - License 2
Mentions: Striking differences were found when myelin breakdown was compared in Atg7 cKO and WT nerves after injury. A significant reduction was seen in injury-induced breakdown of myelin proteins in transected nerves in vivo (Fig. 4, A and B), in cultured nerve segments (Fig. S4 D), and in Schwann cell cultures where Atg7 cKO cells typically retained bloated “cauliflower” morphology for many days due to the persistence of undigested myelin (Fig. 4 C). In transected Atg7 cKO nerves, there was also a striking preservation of noncollapsed myelin (Fig. 4 D), confirming previous results using the autophagy blocker 3-MA (Fig. 3 C).
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.