To go along with a recent post on cell therapies for nerve regeneration, here researchers investigate a different set of mechanisms: "A protein required to regrow injured peripheral nerves has been identified by researchers. ... The finding, in mice, has implications for improving recovery after nerve injury in the extremities. It also opens new avenues of investigation toward triggering nerve regeneration in the central nervous system, notorious for its inability to heal. ... scientists show that a protein called dual leucine zipper kinase (DLK) regulates signals that tell the nerve cell it has been injured - often communicating over distances of several feet. The protein governs whether the neuron turns on its regeneration program. ... 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. ... If an axon is severed somewhere between the cell body in the spinal cord and the muscle, the piece of axon that is no longer connected to the cell body begins to disintegrate. Earlier work showed that DLK helps regulate this axonal degeneration. And in worms and flies, DLK also is known to govern the formation of an axon's growth cone, the structure responsible for extending the tip of a growing axon whether after injury or during development. The formation of the growth cone is an important part of the early, local response of a nerve to injury. But a later response, traveling over greater distances, proves vital for relaying the signals that activate genes promoting regeneration. This late response can happen hours or even days after injury. But in mice, unlike worms and flies, [DLK] is not involved in an axon's early response to injury. Even without DLK, the growth cone forms. But a lack of DLK means the nerve cell body, nestled in the spinal cord far from the injury, doesn't get the message that it's injured. Without the signals relaying the injury message, the cell body doesn't turn on its regeneration program and the growth cone's progress in extending the axon stalls. ... A neuron that has seen a previous injury now has a different regenerative program than one that has never been damaged. We hope to be able to identify what is different between these two neurons - specifically what factors lead to the improved regeneration after a second injury. We have found that activated DLK is one such factor. We would like to activate DLK in a newly injured neuron to see if it has improved regeneration."