An axonal stress response pathway: degenerative and regenerative signaling by DLK

Signaling through the dual leucine zipper-bearing kinase (DLK) is required for injured neurons to initiate new axonal growth; however, activation of this kinase also leads to neuronal degeneration and death in multiple models of injury and neurodegenerative diseases. This has spurred current consideration of DLK as a candidate therapeutic target, and raises a vital question: in what context is DLK a friend or foe to neurons? Here, we review our current understanding of DLK's function and mechanisms in regulating both regenerative and degenerative responses to axonal damage and stress in the nervous system.