The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination.
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.
Karnezis
Tara
T
Neuroimmunology Laboratory, Department of Biochemistry, School of Molecular Sciences, La Trobe University, Bundoora, Victoria 3086, Australia.
Mandemakers
Wim
W
McQualter
Jonathan L
JL
Zheng
Binhai
B
Ho
Peggy P
PP
Jordan
Kelly A
KA
Murray
Belinda M
BM
Barres
Ben
B
Tessier-Lavigne
Marc
M
Bernard
Claude C A
CC
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000473:pathology; D004195:Disease Models, Animal; D004673:Encephalomyelitis, Acute Disseminated / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D016501:Neurites / Q000502:physiology*; D000070798:Nogo Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology; D016622:Silver Staining / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects
D000906:Antibodies; D016207:Cytokines; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat