Nat Neurosci. 2004 Jun 6 Epub 2004 Jun 06
Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, Murray BM, Barres B, Tessier-Lavigne M, Bernard CC.
Neuroimmunology Laboratory, Department of Biochemistry, School of Molecular Sciences, La Trobe University, Bundoora, Victoria 3086, Australia.
Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, California 94305, USA.
Inhibitors associated with CNS myelin are thought to be important in the failure of axons to regenerate after spinal cord injury and in other neurodegenerative disorders.
Here we show that targeting the CNS-specific inhibitor of neurite outgrowth Nogo A by active immunization blunts clinical signs, demyelination and axonal damage associated with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS).
Mice vaccinated against Nogo A produce Nogo-specific antibodies that block the neurite outgrowth inhibitory activity associated with CNS myelin in vitro.
Passive immunization with anti-Nogo IgGs also suppresses EAE.
Our results identify Nogo A as an important determinant of the development of EAE and suggest that its blockade may help to maintain and/or to restore the neuronal integrity of the CNS after autoimmune insult in diseases such as MS.
Our finding that Nogo A is involved in CNS autoimmune demyelination indicates that this molecule may have a far more complex role than has been previously anticipated.