Scientists discover protein needed for regrowing damaged nerves in limbs

Scientists have discovered a crucial protein required for regrowing damaged peripheral nerves – possibly paving the way for expediting recovery in patients who have suffered from nerve injuries in their limbs.

The identification of this protein – known as dual leucine zipper kinase (DLK) – could also further research that may help trigger nerve regrowth in the central nervous system, a feat that has proven almost impossible given the system’s near inability to regrow damaged nerves.

The study, published in the journal Neuron, focused on the differences between the peripheral nervous system and the central nervous system in their responses to nerve damage.  The peripheral nerves – which convey the feeling of touch, as well as telling the muscles to move the arms and legs – have the ability to regenerate if they are severely damaged.

The researchers were already aware that DLK played a role in the body’s response to peripheral nerve damage, but they were not fully aware of how the mechanisms behind nerve regrowth worked.

“We had been studying another aspect of how nerves respond to injury…where you injure a nerve, and the distal portion - the part away from the cell body – will degenerate,” Dr. Aaron DiAntonio, professor of developmental biology at the Washington University School of Medicine in St. Louis and the study’s lead author, told FoxNews.com.  “So we identified the role for this molecule, DLK, as being important for driving that degeneration.  In addition to the part that degenerates, the part that didn’t degenerate would regenerate.  So we wondered: [If DLK] is involved in one part, is it involved in the other part?  Is it involved in regeneration as well?”

In order to better understand how the protein worked, DiAntonio and his team created a group of genetically altered mice that were missing DLK in specific neurons such as their motor neurons, which control the muscles.  The researchers then caused injury to their nerves to see how their bodies would respond.

For a control group of mice with regular amounts of DLK, their peripheral nerves could reconnect with their muscles and regenerate.  But for the mice missing the DLK, their nerve connections did not form 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 said.   “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.”

According to DiAntonio, DLK acts as an alarm system, communicating across long distances to the brain and spinal cord that nerve injury has occurred.  While it is responsible for early degeneration of damaged axons, it also helps to trigger a later response – over a period of hours or even days – that help put the nerve cell back into an embryonic state in which it’s much better at growing.

Because the DLK response sometimes takes a very long time to trigger regrowth, DiAntonio and his team theorized that by promoting the protein’s response, people with nerve injuries in their limbs could hope to have a better chance of recovery and more nerve regeneration.

“Even in the peripheral nervous system, when someone gets an injury to a never in an arm or a leg, the nerve can regrow, but it needs to regrow quickly or else the muscles that normally needs to be innovated by that nerve degenerates,” DiAntonio said.  “So if that nerve doesn’t get back in time, the muscle’s going to degenerate and then it doesn’t matter if [the nerve] regrows.  If we can find a way to promote DLK’s function, even in the case where [the nerves] can regenerate, that might be helpful in cases of say limb injuries.”

While the potential to help patients with nerve damage in their extremities is significant, DiAntonio noted an even larger goal that could be furthered along by this discovery – figuring out how to “turn back on” the central nervous system once it’s been damaged.

“In the central nervous system, potentially with things like stroke, once connections are lost, it’s almost impossible for them to reform,” DiAntonio said.  “It would be very exciting if turning on this [DLK] program in the central nervous system could provide some benefit to those sorts of patients.

“That’s if we can figure out a way to turn it on, and it would certainly take a lot more than just this protein that we discovered and a lot of things would have to happen,” DiAntonio added. “But if after injury, one could quickly get those connections to regrow, that would be the ultimate dream.”