Characterization of the myelin-associated glycoprotein-binding component.
Item
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Title
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Characterization of the myelin-associated glycoprotein-binding component.
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Identifier
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AAI9917642
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identifier
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9917642
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Creator
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de Bellard, Maria Elena.
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Contributor
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Adviser: Marie T. Filbin
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Date
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1999
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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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Biology, Neuroscience | Biology, Cell | Biology, Molecular
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Abstract
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The adult mammalian CNS does not regenerate after injury due to several factors, the most outstanding, the presence of myelin-specific inhibitors of axonal growth. Myelin-associated glycoprotein (MAG) is a potent inhibitor of axonal regeneration from both cerebellar and DRG neurons. In contrast, MAG promotes axonal growth from newborn DRG neurons. Here, we show that to date of all the neurons tested, a postnatal switch in response is only observed for DRG neurons; MAG inhibits axonal growth from retinal, SCG, spinal and hippocampal neurons of all postnatal ages. Furthermore, MAG binds to neurons, from which it promotes and inhibits outgrowth, in a sialic acid-dependent, trypsin-sensitive manner. Hence, the interaction is via a sialoglycoprotein. Importantly, both inhibition and promotion of neurite outgrowth by MAG was reduced, or abolished, either by desialylation or by including small sialic acid-bearing sugars in the cultures. MAG contributes to the inhibitory properties of myelin both in vitro and in vivo. When myelin from MAG-/- mice is used as a substrate, neurites from postnatal cerebellar and from neonatal DRG neurons grow twice as long on MAG+/+ myelin relative to MAG-/- myelin. In addition, when mice are genetically engineered to express MAG in Schwann cells during PNS regeneration, the growth of axons after injury was dramatically reduced in the transgenic compared with the control mice. Attempts to isolate the neuronal sialoglycoprotein with which MAG interacts, by purifying MAG binding partners from different types of neurons using soluble MAG-Fc, indicated that MAG binds to at least three proteins of approximately 190 and 250kD. The p190 band corresponds to two proteins, one of which is a GPI-linked sialoglycoprotein. Together these results indicate that MAG can significantly contribute to the lack of axonal regeneration given by myelin inhibitors present after injury, and that partial reversal of this inhibition can be achieved by desialylation or adding small sialic acid sugars. It has been the goal of these studies to provide some clues to how lack of regeneration takes place in the nervous system and how to circumvent this problem in the CNS.
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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.
