Yale Researchers Identify Gene and Protein That Stops Spinal Cord and Brain Regrowth After Nervous System Injury

Reversing brain and spinal cord injuries may soon be possible with the discovery of a gene and protein responsible for stopping axon regrowth, Yale researchers say.

Brain and spinal cord axons can grow after injury if provided with an adequate environment, but the natural adult brain environment contains substances which inhibit axon regeneration. One of these inhibitors is the Nogo protein.

“We have identified the gene and protein responsible for this Nogo activity,” said Stephen M. Strittmatter, M.D., associate professor of neurology and of neurobiology at Yale School of Medicine. “Our work suggests that the Nogo protein is an important and selective blocker of axon regeneration in the brain after central nervous system injury.”

Published in the January 27 issue of Nature, Strittmatter’s study shows that Nogo protein generated in the laboratory stops axon growth. In addition, the protein is found exclusively in those areas of the brain which are most hostile to axon growth. Future experiments will determine whether this is the major inhibitor of axon regeneration in the brain or if it is one of several inhibitors.

After many adult nervous system injuries, the nerve cells survive but their connecting axons are severed and function is lost. Outside the brain and spinal cord, these connections usually grow back and recovery is excellent.

Inside the brain and spinal cord, very little axon regrowth occurs after injury and the clinical prognosis for recovery of function is poor. A clear example of this is human spinal cord injury.

In addition to identifying the gene and protein, the team also found that the inhibitory activity is localized to a discrete portion of Nogo. Because this inhibitory portion is less than 10 percent of the entire Nogo protein, Strittamatter says, the identification and design of inhibitors of Nogo action should be greatly facilitated.

“If those inhibitors based on Nogo can be developed, the failure of axon regeneration and functional recovery after many brain and spinal injuries might be reversed,” said Strittmatter.

Strittmatter’s research team in the Department of Neurology at Yale included Tadzia GrandPre and Fumio Nakamura, M.D. The work was completed in collaboration with Timothy Vartanian, M.D. of the Department of Neurology at Beth Israel Deaconess Medical Center Harvard Institutes of Medicine.

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Karen N. Peart: karen.peart@yale.edu, 203-432-1326