Regulating axon growth within the postnatal central nervous system.
As neuronal development enters its final stages, axonal growth is restricted. Recent work indicates that several myelin-derived proteins, Nogo, MAG and OMgp, play a critical role in restricting axonal growth in the mature central nervous system (CNS). These proteins function by binding to an axonal NgR protein that limits axonal growth by activating Rho in neurons. Hypoxic conditions during the later stages of neuronal development have a prominent effect on oligodendrocytes and hence on the expression of these axon growth inhibitors. Reduced expression of these proteins caused by the developmental hypoxia, or direct blockade of the myelin inhibitor pathways in the adult CNS leads to axonal sprouting and the formation of new neuronal connections. The regulation of axonal growth, sprouting and connections in the postnatal brain by myelin proteins is an area of important investigation and potential therapeutic intervention.
Hu
Fenghua
F
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA.
Strittmatter
Stephen M
SM
D000818:Animals; D001369:Axons / Q000502:physiology*; D002490:Central Nervous System / Q000254:growth & development* / Q000502:physiology; D058851:GPI-Linked Proteins; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D009185:Myelin Proteins / Q000502:physiology; D018992:Myelin-Associated Glycoprotein / Q000502:physiology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D020800:Receptor, Nerve Growth Factor / Q000502:physiology; D011956:Receptors, Cell Surface
D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C482293:LINGO1 protein, human; C571326:MOG protein, human; D008565:Membrane Proteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C560528:OMG protein, human; C560529:Omg protein, mouse; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse