The Francis Crick Institute
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Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

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journal contribution
posted on 2020-07-28, 13:01 authored by Jose A Gomez-Sanchez, Lucy Carty, Marta Iruarrizaga-Lejarreta, Marta Palomo-Irigoyen, Marta Varela-Rey, Megan Griffith, Janina Hantke, Nuria Macias-Camara, Mikel Azkargorta, Igor Aurrekoetxea, Virginia Gutiérrez De Juan, Harold BJ Jefferies, Patricia Aspichueta, Félix Elortza, Ana M Aransay, María L Martínez-Chantar, Frank Baas, José M Mato, Rhona Mirsky, Ashwin Woodhoo, Kristján R Jessen
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.