A role for myelin-associated glycoprotein as an inhibitor of axonal regeneration.
Item
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Title
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A role for myelin-associated glycoprotein as an inhibitor of axonal regeneration.
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Identifier
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AAI9720121
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identifier
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9720121
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Creator
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Mukhopadhyay, Gitali.
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Contributor
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Adviser: Marie T. Filbin
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry | Biology, Neuroscience
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Abstract
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Following nerve injury, axons in the CNS do not normally regenerate. It has been shown that CNS myelin inhibits neurite outgrowth. However the precise nature of the molecules responsible for this effect is not known. In the nervous system myelin-associated glycoprotein (MAG), a well characterized transmembrane glycoprotein has been shown to promote neurite outgrowth from newborn dorsal root ganglion (DRG) neurons. Here, we demonstrate that MAG expressed by Chinese hamster ovary (CHO) cells can inhibit neurite outgrowth from cerebellar neurons of all post-natal ages and PND3 (postnatal days) through adult DRG neurons. Both the large (L-MAG) and small (S-MAG) isoforms of MAG behave in this manner. In addition, it has been shown that MAG binds to sialoglycoproteins on the surface of neurons and inhibition/promotion by MAG depends directly or indirectly on this binding. To begin to map the sialic acid binding site in MAG, arginine 118 (R118), a conserved amino acid among the family of molecules termed the Sialoadhesins, to which MAG belongs, was mutated to either alanine (R118A) or aspartic acid (R118D). We found that MAG mutated at R118, when expressed in CHO cells, still inhibited neurite outgrowth. Therefore, we suggest that sialic acid binding of MAG to neurons is necessary but insufficient to affect axonal regeneration. It has been reported that PNS myelin, unlike CNS myelin is permissive for neurite outgrowth. Using various concentrations of purified PNS myelin as a substrate, we demonstrate that this membrane is also inhibitory for axonal regeneration.;In conclusion, besides its putative role in the initiation of myelination, we have identified additional role for MAG as an inhibitor of axonal regeneration. This inhibitory effect of MAG may be responsible, in part, for the lack of CNS nerve regeneration in vivo.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
