Protein Discovered That Regrows Injured Nerves in Limbs

By Chelsea Whyte on June 21, 2012 9:15 PM EDT

protein regrowing nerves
These are images of axon regeneration in mice two weeks after injury to the hind leg’s sciatic nerve. On the left, axons (green) of a normal mouse have regrown to their targets (red) in the muscle. On the right, a mouse lacking DLK shows no axons have regenerated, even after two weeks. (Photo: Jung Eun Shin)

The key to regrowing injured nerves lies in a signaling protein, according to new research from Washington University School of Medicine in St. Louis.

The study, based on a mouse model using mutant mice missing the crucial protein, found that a protein called dual leucine zipper kinase (DLK) regulates signals that tell the nerve cell it has been injured and then governs whether the neuron turns on its regeneration program.

DLK only works in peripheral nerves - those that provide the sense of touch and drive muscles that move arms and legs, hands and feet - but this research may lead to the possibility of triggering nerve regeneration in the central nervous system, notorious for its inability to heal.

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"DLK is a key molecule linking an injury to the nerve's response to that injury, allowing the nerve to regenerate," said lead author Aaron DiAntonio. "How does an injured nerve know that it is injured? How does it take that information and turn on a regenerative program and regrow connections? And why does only the peripheral nervous system respond this way, while the central nervous system does not? We think DLK is part of the answer."

To understand how DLK works, DiAntonio and his team created a set of genetically altered mice missing the important protein in motor neurons, and then caused them injury to see how their body would react.

In a control group of mice with DLK, their peripheral nerves could reconnect with their muscles and regenerate. But without the DLK, the altered mice did not form nerve connections in either the peripheral or central nervous system.

"So it turns out in our mutants that are missing DLK, now the peripheral branch looks a lot like the central branch," DiAntonio told Fox News.   "A central branch when it gets injured somehow can't convey the message back to the neuronal cell body that it's been injured.  In the DLK mutant, that's exactly what happens in the periphery - when it gets injured it can't convey the message back to the cell body either."

The main body, or 'brain', of peripheral nerves lives in the spinal cord. From there, the nerves extend long, spindly branches known as axons that reach out to muscles and the tips of fingers and toes. If the axon is severed or damaged, DLK acts like an alarm to tell the body to begin breaking down the axon, and then tells the part still connected to the spinal cord to regrow or extend.

It has also been proven that axons injured more than once regrow faster than axons that receive a first-time injury. This may be due to the presence of DLK left over from the first injury, which expedites regeneration, reports Latinos Post.

"Since this sort of signaling doesn't appear to happen in the central nervous system, it's possible these nerves don't 'know' when they are injured," DiAntonio says. "It's an exciting idea - but not at all proven - that activating DLK in the central nervous system could promote its regeneration."

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