Nogo: a molecular determinant of axonal growth and regeneration.
Following injury, axons of the adult mammalian central nervous system (CNS) fail to regenerate. As a result, CNS trauma generally results in severe and persistent functional deficits. The inability of CNS axons to regenerate is largely associated with nonneuronal aspects of the CNS environment that are inhibitory to axonal elongation. This inhibition is mediated by the glial scar, including reactive astrocytes, and by the myelin-associated neurite outgrowth inhibitors chondroitin sulfate proteoglycans, myelin-associated glycoprotein, and Nogo. Nogo is an integral membrane protein that localizes to CNS, but not peripheral nervous system, myelin. In vitro characterization of Nogo has demonstrated its function as a potent inhibitor of axon elongation. In vivo neutralization of Nogo activity results in enhanced axonal regeneration and functional recovery following CNS injury as well as increased plasticity in uninjured CNS fibers. These findings suggest that Nogo may be a major contributor to the nonpermissive nature of the CNS environment.
Grandpré
T
T
Department of Neurology, Yale University School of Medicine New Haven, Connecticut 06520, USA.
Strittmatter
S M
SM
D000818:Animals; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000502:physiology / Q000503:physiopathology; D001930:Brain Injuries / Q000503:physiopathology; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D008322:Mammals; D008959:Models, Neurological; D009185:Myelin Proteins / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity; D000070798:Nogo Proteins
D006131:Growth Inhibitors; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human