title: The role of Nogo-A in axonal plasticity, regrowth and repair.
abstract: Axonal damage leads to permanent deficits in the adult central nervous system (CNS) not only because of the weak intrinsic ability of adult neurons to activate their growth program but importantly also because of the presence of specific growth inhibitors in the CNS tissue and the environment of the damaged axons. The well-studied myelin-derived protein Nogo-A is involved in various cellular and molecular events contributing to the failure of CNS axons to regrow and reconnect after transection. Recent studies have shown that, by acting in a negative way on the cytoskeleton and on the growth program of axotomized neurons, Nogo-A exerts fast and chronic inhibitory effects on neurite outgrowth. On the other hand, the blockade of Nogo-A results in a marked enhancement of compensatory and regenerative axonal extension in vivo; this enhancement is often paralleled by significant functional recovery, for example, of locomotion or skilled forelimb reaching after spinal cord or stroke lesions in rats and monkeys. Surprisingly, the blockade of Nogo-A or its receptor NgR in the hippocampus has recently been demonstrated to enhance long-term potentiation. A role of Nogo-A in synaptic plasticity/stability might therefore represent an additional, new and important aspect of CNS circuit remodeling. Function-blocking anti-Nogo-A antibodies are currently being tested in a clinical trial for improved outcome after spinal cord injury.
authors.affiliation: Brain Research Institute, University of Zürich/ETH, Department of Health Sciences and Technology ETH Zürich, Winterthurerstrasse 190, Room 55J34a, 8057 Zürich, Switzerland. pernet@hifo.uzh.ch
authors.forename: Vincent
authors.initials: V
authors.lastname: Pernet
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009185:Myelin Proteins / Q000378:metabolism*; D009415:Nerve Net / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D000070798:Nogo Proteins; D014945:Wound Healing
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat