Myelin-Associated Glycoprotein Inhibits Schwann Cell Migration and Induces Their Death

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Nagarathnamma ChaudhryMarie T Filbin

Abstract

Remyelination of CNS axons by Schwann cells (SCs) is not efficient, in part due to the poor migration of SCs into the adult CNS. Although it is known that migrating SCs avoid white matter tracts, the molecular mechanisms underlying this exclusion have never been elucidated. We now demonstrate that myelin-associated glycoprotein (MAG), a well known inhibitor of neurite outgrowth, inhibits rat SC migration and induces their death via γ-secretase-dependent regulated intramembrane proteolysis of the p75 neurotrophin receptor (also known as p75 cleavage). Blocking p75 cleavage using inhibitor X (Inh X), a compound that inhibits γ-secretase activity before exposing to MAG or CNS myelin improves SC migration and survival in vitro Furthermore, mouse SCs pretreated with Inh X migrate extensively in the demyelinated mouse spinal cord and remyelinate axons. These results suggest a novel role for MAG/myelin in poor SC-myelin interaction and identify p75 cleavage as a mechanism that can be therapeutically targeted to enhance SC-mediated axon remyelination in the adult CNS.SIGNIFICANCE STATEMENT Numerous studies have used Schwann cells, the myelin-making cells of the peripheral nervous system to remyelinate adult CNS axons. Indeed, these tra...Continue Reading

Citations

Feb 7, 2020·Glia·Beatriz Garcia-Diaz, Anne Baron-Van Evercooren
May 14, 2020·Brain Sciences·Marilisa BoscarinoGiovanni Assenza
Apr 24, 2019·Acta Neuropathologica·Beatriz Garcia-DiazAnne Baron-Van Evercooren
Apr 14, 2020·Developmental Neurobiology·Emma R WilsonM Laura Feltri
Oct 19, 2020·Journal of Neuroscience Research·Sophie Charlotte RhodeTim Ruhl

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