More MS news articles for June 2002

Nogo Receptor Blocker May Stimulate Axon Regeneration After CNS Injury

http://www.medscape.com/viewarticle/436771

Jun 17, 2002
NEW YORK (Reuters Health)

Multiple inhibitors of neurite outgrowth act through the same signaling pathway, which is mediated by the Nogo receptor, the results of in vitro studies suggest. This news may help researchers develop drugs to prevent paralysis caused by injury to the CNS, investigators report in the June 16th advance online publication of Nature.

Dr. Zhigang He, of Harvard Medical School in Boston, and associates looked for glycosylphosphatidylinositol-linked proteins in myelin that could serve as inhibitors of neurite outgrowth. They observed that oligodendrocyte-myelin glycoprotein (OMgp), isolated from bovine white matter, caused growth cone collapse in embryonic chicken dorsal root ganglia.

The inhibitory activity was similar to that associated with the alkaline phosphatase fusion protein Nogo-A and greater than that associated with myelin-associated glycoprotein. Further research showed that the Nogo receptor binds OMgp with high affinity. The domain of OMgp containing a leucine-rich repeat, which binds to the Nogo receptor, is similar to that in NgR. This suggests that the two proteins act independently, the authors note.

"This molecule [OMgp] is particularly interesting," Dr. He told Reuters Health. As opposed to Nogo-A, OMgp is a surface molecule, which makes it a more attractive target for stopping nerve cell growth inhibition, he explained.

Dr. He believes that the two proteins, Nogo-A and OMgp, "account for the majority of the inhibitory activity of the receptor."

Therefore, "if we want to design a therapeutic strategy, the ideal target is the Nogo receptor," perhaps by way of an antibody or small molecule to block the receptor function, Dr. He said. This strategy would be simpler than using antibodies to both Nogo-A and OMgp.

Last month, Yale University researchers described a peptide antagonist of the Nogo receptor (see Reuters Health report, May 29.) Dr. He called this report "a proof of principle, that if you can block this receptor function, you may be able to stimulate axon regeneration."

The problem with that approach, he said, is that "we don't know if that peptide [NEP1-40] will bind OMgp or not, since OMgp and Nogo-A bind to different regions of the receptor."

Nature advance online publication, June 16, 2002. http://nature.com/nature/
 

© 2002 Reuters Ltd