1. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.
- Author
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Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo-Irigoyen M, Varela-Rey M, Griffith M, Hantke J, Macias-Camara N, Azkargorta M, Aurrekoetxea I, De Juan VG, Jefferies HB, Aspichueta P, Elortza F, Aransay AM, Martínez-Chantar ML, Baas F, Mato JM, Mirsky R, Woodhoo A, and Jessen KR
- Subjects
- Animals, Cells, Cultured, JNK Mitogen-Activated Protein Kinases metabolism, Lipid Metabolism, Mice, Transgenic, Myelin Sheath physiology, Peripheral Nerve Injuries enzymology, Proto-Oncogene Proteins c-jun metabolism, Sciatic Nerve pathology, TOR Serine-Threonine Kinases metabolism, Wallerian Degeneration pathology, Autophagy, Myelin Sheath pathology, Peripheral Nerve Injuries pathology
- Abstract
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., (© 2015 Gomez-Sanchez et al.)
- Published
- 2015
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