Axonal protective effects of the myelin-associated glycoprotein.
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.
Nguyen
Thien
T
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. tnguyena@jhmi.edu
Mehta
Niraj R
NR
Conant
Katherine
K
Kim
Kee-Jun
KJ
Jones
Melina
M
Calabresi
Peter A
PA
Melli
Giorgia
G
Hoke
Ahmet
A
Schnaar
Ronald L
RL
Ming
Guo-Li
GL
Song
Hongjun
H
Keswani
Sanjay C
SC
Griffin
John W
JW
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
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