NG2: a component of the glial scar that inhibits axon growth

NG2 is a high‐molecular‐weight chondroitin sulphate proteoglycan found on the surfaces of oligodendrocyte precursor cells (OPCs). Here we review the history and biology of OPCs with an emphasis on their functions after experimentally induced CNS injury. Injury to brain or spinal cord results in the rapid accumulation of NG2‐expressing OPCs in the glial scar that forms at the injury site. The glial scar is considered a biochemical and physical barrier to successful axon regeneration and the functional properties of NG2 suggest that it, along with other macromolecules, participates in the creation of this growth‐inhibitory environment. NG2 is an important target for therapies designed to promote successful axon regrowth.

[1]  Richard Reynolds,et al.  NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS , 2003, Molecular and Cellular Neuroscience.

[2]  Mark H. Tuszynski,et al.  NG2 Is a Major Chondroitin Sulfate Proteoglycan Produced after Spinal Cord Injury and Is Expressed by Macrophages and Oligodendrocyte Progenitors , 2002, The Journal of Neuroscience.

[3]  J. Levine,et al.  Multiple Regions of the NG2 Proteoglycan Inhibit Neurite Growth and Induce Growth Cone Collapse , 2003, The Journal of Neuroscience.

[4]  J. Silver,et al.  Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  Robert H Miller,et al.  Density-Dependent Feedback Inhibition of Oligodendrocyte Precursor Expansion , 1996, The Journal of Neuroscience.

[6]  M. Noble,et al.  In vitro analysis of the origin and maintenance of O-2Aadult progenitor cells , 1992, The Journal of cell biology.

[7]  J. Levine,et al.  Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  A. Rosenthal,et al.  A novel repeat in the melanoma‐associated chondroitin sulfate proteoglycan defines a new protein family , 2002, FEBS letters.

[9]  A. Nishiyama,et al.  Generation of truncated forms of the NG2 proteoglycan by cell surface proteolysis. , 1995, Molecular biology of the cell.

[10]  W. Stallcup,et al.  Bipotential glial precursor cells of the optic nerve express the NG2 proteoglycan , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  A. Nishiyama,et al.  Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion , 2001, Glia.

[12]  W. Stallcup,et al.  High-affinity Binding of Basic Fibroblast Growth Factor and Platelet-derived Growth Factor-AA to the Core Protein of the NG2 Proteoglycan* , 1999, The Journal of Biological Chemistry.

[13]  J. Levine.  Increased expression of the NG2 chondroitin-sulfate proteoglycan after brain injury , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  W. Mandemakers,et al.  An Oligodendrocyte Lineage-Specific Semaphorin, Sema5A, Inhibits Axon Growth by Retinal Ganglion Cells , 2004, The Journal of Neuroscience.

[15]  J. Levine,et al.  Development and differentiation of glial precursor cells in the rat cerebellum , 1993, Glia.

[16]  J. Fawcett,et al.  Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC , 2001, Nature Neuroscience.

[17]  M. Berry,et al.  Synantocytes: New functions for novel NG2 expressing glia , 2002, Journal of neurocytology.

[18]  Richard Reynolds,et al.  The oligodendrocyte precursor cell in health and disease , 2001, Trends in Neurosciences.

[19]  B. Barres,et al.  Notch Receptor Activation Inhibits Oligodendrocyte Differentiation , 1998, Neuron.

[20]  J. Levine,et al.  Oligodendrocyte precursor cells: Reactive cells that inhibit axon growth and regeneration , 2002, Journal of neurocytology.

[21]  W. Stallcup,et al.  Chondroitin sulfate and cytoplasmic domain-dependent membrane targeting of the NG2 proteoglycan promotes retraction fiber formation and cell polarization. , 2001, Journal of cell science.

[22]  J. Levine,et al.  Inhibition of Axon Growth by Oligodendrocyte Precursor Cells , 2002, Molecular and Cellular Neuroscience.

[23]  M. Raff.  Glial cell diversification in the rat optic nerve. , 1989, Science.

[24]  M. Berry,et al.  Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white matter , 1999, Glia.

[25]  J. Levine,et al.  Plasticity of developing cerebellar cells in vitro studied with antibodies against the NG2 antigen , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  H. Eichenbaum,et al.  Spatial and behavioral correlates of hippocampal neuronal activity , 1989 .

[27]  J. Maisin,et al.  The beta astrocyte: a newly recognized radiosensitive glial cell type in the cerebral cortex , 1982, Journal of neurocytology.

[28]  P. Anderson,et al.  Correlation between Putative Inhibitory Molecules at the Dorsal Root Entry Zone and Failure of Dorsal Root Axonal Regeneration , 2001, Molecular and Cellular Neuroscience.

[29]  J. Fawcett,et al.  Chondroitin sulphate proteoglycans in the CNS injury response. , 2002, Progress in brain research.

[30]  J. Silver,et al.  Robust Regeneration of Adult Sensory Axons in Degenerating White Matter of the Adult Rat Spinal Cord , 1999, The Journal of Neuroscience.

[31]  B. Barres,et al.  Purification and Characterization of Adult Oligodendrocyte Precursor Cells from the Rat Optic Nerve , 1998, The Journal of Neuroscience.

[32]  Masahiko Watanabe,et al.  Identity, distribution, and development of polydendrocytes: NG2-expressing glial cells , 2002, Journal of neurocytology.

[33]  E. Baetge,et al.  Antisera specific for cell lines with mixed neuronal and glial properties. , 1981, Developmental biology.

[34]  J. Fawcett,et al.  The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain , 2004, Neuroscience.

[35]  James W. Fawcett,et al.  Chondroitinase ABC promotes functional recovery after spinal cord injury , 2002, Nature.

[36]  R Reynolds,et al.  NG2‐expressing cells in the central nervous system: Are they oligodendroglial progenitors? , 2000, Journal of neuroscience research.

[37]  J. Prince,et al.  The primary structure of NG2, a novel membrane-spanning proteoglycan , 1991, The Journal of cell biology.

[38]  J. Levine,et al.  A light and electron microscopic study of NG2 chondroitin sulfate proteoglycan-positive oligodendrocyte precursor cells in the normal and kainate-lesioned rat hippocampus , 1999, Neuroscience.