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Nogo in multiple sclerosis: growing roles of a growth inhibitor.

Abstract
In recent years, knowledge about the physiological functions of the Nogo-A protein has grown considerably, and this molecule has evolved from being one of the most important axonal regrowth inhibitors present in central nervous system (CNS) myelin, to several other potentially important roles in different areas such as nervous system development, epilepsy, vascular physiology, muscle pathology and CNS tumors. Therapeutically, targeting the Nogo-A protein by means of the immune response has been tried in an attempt to block neurite growth inhibition and promote regeneration in spinal cord injury models; the immune response to Nogo-A, however, has not been extensively studied. We propose to review recent evidence that Nogo-A may also play an important role in autoimmune demyelinating diseases such as experimental autoimmune encephalomyelitis and multiple sclerosis, including that Nogo-66 derived epitopes are encephalitogenic antigens in susceptible mouse strains, and that the immune response to Nogo-66 antigens includes both strong T cell and B cell activation, with epitope spreading of the antibody response to other myelin molecules. In CNS immunotherapy, careful targeting of neural self-antigens is a prerequisite in order to avoid unexpected deleterious effects, and increasing knowledge about the immune response to Nogo-A may provide a safe basis for the development of relevant therapeutic alternatives for several neurological conditions.
AuthorsPaulo Fontoura, Lawrence Steinman
JournalJournal of the neurological sciences (J Neurol Sci) Vol. 245 Issue 1-2 Pg. 201-10 (Jun 15 2006) ISSN: 0022-510X [Print] Netherlands
PMID16682057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Myelin Proteins
  • Nogo Proteins
  • RTN4 protein, human
  • Rtn4 protein, mouse
Topics
  • Animals
  • Brain (metabolism, pathology)
  • Humans
  • Immune System (metabolism)
  • Models, Biological
  • Multiple Sclerosis (genetics, immunology, metabolism)
  • Myelin Proteins (genetics, metabolism)
  • Nogo Proteins

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