The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination

Tara Karnezis, Wim Mandemakers, Jonathan L. McQualter, Binhai Zheng, Peggy P. Ho, Kelly A. Jordan, Belinda M. Murray, Ben Barres, Marc Tessier-Lavigne, Claude C.A. Bernard*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

214 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)736-744
Number of pages9
JournalNature Neuroscience
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 2004
Externally publishedYes

Bibliographical note

Funding Information:
We thank A. Slavin and S. Baranzini for suggestions and reviewing the manuscript; R. Sobel for help with histology; S. Dunn for the MBP-specific transgenic mice; L. Steinman and P. Fontoura for sharing unpublished results on Nogo A and L. Hazelwood and L. Lee for technical assistance. The work done in C.C.A.B.’s laboratory was supported by grants from the National Health and Medical Research Council of Australia and the US National Multiple Sclerosis Society, as well as a generous donation from Towards a Cure–MS, Australia. W.M. is a recipient of a US National Multiple Sclerosis Society Fellowship. B.Z. is a recipient of a Helen Hay Whitney Fellowship. B.B.’s laboratory is supported by a grant from the National Eye Institute (R01 EY10257) and M.T.-L.’s laboratory by a grant from the International Spinal Research trust. M.T.-L. is an Investigator of the Howard Hughes Medical Institute.

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