Axonal Protective Effects of the Myelin-Associated Glycoprotein

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J Neurosci. 2009 Jan 21;29(3):630-637.

Axonal Protective Effects of the Myelin-Associated Glycoprotein.

Nguyen T, Mehta NR, Conant K, Kim KJ, M, Calabresi PA, Melli G,

Hoke A, Schnaar RL, Ming GL, Song H, Keswani SC, JW.

Departments of Neurology, Neuroscience, and Pathology, The s

Hopkins University School of Medicine, Baltimore, land 21287,

Department of Pharmacology and Institute for Cell Engineering, The

s Hopkins University, Baltimore, land 21205, and Department

of Microbiology, Molecular Genetics and Immunology, University of

Kansas Medical Center, Kansas City, Kansas 66160.

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.