WESTPORT, CT (Reuters Health) Jan 17 - An interaction between the protein Nogo, which is made by myelinating cells in the central nervous system (CNS), and its receptor could be the key step that inhibits the regeneration of axons after brain or spinal cord injury, according to a report in the January 18th issue of Nature.
Interrupting this interaction could restore the ability of axons to regenerate, Dr. Stephen M. Strittmatter and colleagues at Yale University School of Medicine, in New Haven, Connecticut, speculate in the report. Their current identification of a Nogo receptor mediator "should greatly facilitate the development of agents with pharmaceutical potential in a diverse group of neurological conditions, such as spinal-cord injury, brain trauma, stroke affecting white matter and chronic, progressive multiple sclerosis."
"About a year ago...our lab and others discovered Nogo," Dr. Strittmatter told Reuters Health. Now, his group describes the discovery of an extracellular receptor for Nogo that, at least in vitro, is a "potent inhibitor" of axonal regeneration.
The receptor, which binds to the 66-amino acid extracellular domain of Nogo (Nogo-66), is "a brain-specific, leucine-rich-repeat protein," the scientists report in the journal. Cleavage of the interaction between Nogo and this receptor renders cultured axons insensitive to the growth-inhibiting effects of Nogo. And expression of the Nogo-66 receptor is sufficient to restore inhibition.
Since the interaction between Nogo-66 and its receptor occurs outside the cell, it represents a "real target" for the development of small drugs that could enhance axonal growth in the CNS, Dr. Strittmatter explained. He noted that other investigators have identified antibodies to Nogo that enhance recovery after CNS injury in rats. Drugs that target the interaction between Nogo-66 and its receptor will likely be more potent anti-Nogo agents, having an even greater effect on CNS injury recovery, he added.
The Yale investigators are now attempting to develop agents to block the binding of Nogo-66 with its receptor. They are also trying to develop Nogo and Nogo receptor knockouts to help determine the true biologic significance of Nogo. An important question that still remains, Dr. Strittmatter added, is the importance of Nogo and Nogo receptor in vivo.
2000 Reuters Ltd.