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A Hypothesis About the Relationship of Myelin-Associated Glycoprotein’s Function in Myelinated Axons to its Capacity to Inhibit Neurite Outgrowth

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Abstract

The myelin-associated glycoprotein (MAG) is selectively localized in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths suggesting that it functions in glia–axon interactions in the PNS and CNS, and this is supported by much experimental evidence. In addition, MAG is now well known as one of several white matter inhibitors of neurite outgrowth in vitro and axonal regeneration in vivo, and this latter area of research has provided a substantial amount of information about neuronal receptors or receptor complexes for MAG. This article makes the hypothesis that the capacity of MAG to inhibit outgrowth of immature developing or regenerating neurites is an aberration of its normal physiological function to promote the maturation, maintenance, and survival of myelinated axons. The overview summarizes the literature on the function of MAG in PNS and CNS myelin sheaths and its role as an inhibitor of neurite outgrowth to put this hypothesis into perspective. Additional research is needed to determine if receptors and signaling systems similar to those responsible for MAG inhibition of neurite outgrowth also promote the maturation, maintenance, and survival of myelinated axons as hypothesized here, or if substantially different MAG-mediated signaling mechanisms are operative at the glia–axon junction.

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Abbreviations

MAG:

Myelin-associated glycoprotein

MS:

Multiple sclerosis

NgR:

Nogo receptor

p75NtR:

p75 Neurotrophin receptor

OMgp:

Oligodendrocyte-Myelin glycoprotein

2,3- or 2,6-SA:

α2,3- or α2,6-linked sialic acid

siglec:

Sialic acid-binding immunoglobulin-like lectin

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Acknowledgments

This article is dedicated to George DeVries, a long time colleague and good friend. The subject is very appropriate because George followed the MAG story closely as it evolved over the years. Preparation of this review and covered research from our laboratory were supported by the Intramural Research Program of NINDS, NIH.

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  1. National Institute of Neurological Disorders and Stroke, NIH, 5625 Fishers Lane, Rm. 4S-30, MSC 9407, Bethesda, MD, 20892, USA

    Richard H. Quarles

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Correspondence to Richard H. Quarles.

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Special issue article in honor of Dr. George DeVries.

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Quarles, R.H. A Hypothesis About the Relationship of Myelin-Associated Glycoprotein’s Function in Myelinated Axons to its Capacity to Inhibit Neurite Outgrowth. Neurochem Res 34, 79–86 (2009). https://doi.org/10.1007/s11064-008-9668-y

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