title: Axonal protective effects of the myelin-associated glycoprotein.
abstract: Progressive axonal degeneration follows demyelination in many neurological diseases, including multiple sclerosis and inherited demyelinating neuropathies, such as Charcot-Marie-Tooth disease. One glial molecule, the myelin-associated glycoprotein (MAG), located in the adaxonal plasmalemma of myelin-producing cells, is known to signal to the axon and to modulate axonal caliber through phosphorylation of axonal neurofilament proteins. This report establishes for the first time that MAG also promotes resistance to axonal injury and prevents axonal degeneration both in cell culture and in vivo. This effect on axonal stability depends on the RGD domain around arginine 118 in the extracellular portion of MAG, but it is independent of Nogo signaling in the axon. Exploiting this pathway may lead to therapeutic strategies for neurological diseases characterized by axonal loss.
authors.affiliation: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. tnguyena@jhmi.edu
authors.forename: Thien
authors.initials: T
authors.lastname: Nguyen
authors.forename: Niraj R
authors.initials: NR
authors.lastname: Mehta
authors.forename: Katherine
authors.initials: K
authors.lastname: Conant
authors.forename: Kee-Jun
authors.initials: KJ
authors.lastname: Kim
authors.forename: Melina
authors.initials: M
authors.lastname: Jones
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Giorgia
authors.initials: G
authors.lastname: Melli
authors.forename: Ahmet
authors.initials: A
authors.lastname: Hoke
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Schnaar
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.forename: Sanjay C
authors.initials: SC
authors.lastname: Keswani
authors.forename: John W
authors.initials: JW
authors.lastname: Griffin
mesh_terms: D020106:Acrylamide / Q000633:toxicity; D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D016297:Mutagenesis, Site-Directed / Q000379:methods; D009185:Myelin Proteins / Q000172:deficiency; D018992:Myelin-Associated Glycoprotein / Q000172:deficiency / Q000502:physiology* / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D000070816:Nogo Receptor 1; D054801:Phosphoinositide Phospholipase C / Q000633:toxicity; D051381:Rats; D011956:Receptors, Cell Surface / Q000172:deficiency; D013119:Spinal Cord Injuries / Q000150:complications; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse; D014404:Tubulin; D050257:Tubulin Modulators; D020106:Acrylamide; D014750:Vincristine; D054801:Phosphoinositide Phospholipase C