Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves
نویسندگان
چکیده
Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. 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.
منابع مشابه
Myelinophagy: Schwann cells dine in
When nerve injury occurs, the axon and myelin fragments distal to the injury site have to be cleared away before repair. In this issue, Gomez-Sanchez et al. (2015; J. Cell Biol. http://dx.doi.org/10.1083/jcb.201503019) find that clearance of the damaged myelin within Schwann cells occurs not by phagocytosis but rather via selective autophagy, in a process they term "myelinophagy."
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