DLK: The “Preconditioning” Signal for Axon Regeneration?

DLK: The “Preconditioning” Signal for Axon Regeneration?

In this issue of Neuron, Shin et al. (2012) show that the dual leucine zipper kinase (DLK) is responsible for the retrograde injury signal in spinal sensory and motor neurons. DLK is required for the accelerated regeneration seen after axotomy and for the improved regeneration seen after a conditioning injury. DLK KO axons have severely reduced axon regeneration in vivo.

The DLK-1 Kinase Promotes mRNA Stability and Local Translation in C. elegans Synapses and Axon Regeneration

Growth cone guidance and synaptic plasticity involve dynamic local changes in proteins at axons and dendrites. The Dual-Leucine zipper Kinase MAPKKK (DLK) has been previously implicated in synaptogenesis and axon outgrowth in C. elegans and other animals. Here we show that in C. elegans DLK-1 regulates not only proper synapse formation and axon morphology but also axon regeneration by influenci...

Dual Leucine Zipper Kinase Is Required for Retrograde Injury Signaling and Axonal Regeneration

Here we demonstrate that the dual leucine zipper kinase (DLK) promotes robust regeneration of peripheral axons after nerve injury in mice. Peripheral axon regeneration is accelerated by prior injury; however, DLK KO neurons do not respond to a preconditioning lesion with enhanced regeneration in vivo or in vitro. Assays for activation of transcription factors in injury-induced proregenerative p...

Releasing the Inner Inhibition for Axon Regeneration

The adult mammalian central nervous system exhibits restricted regenerative potential. Chen et al. (2011) and El Bejjani and Hammarlund (2012) used Caenorhabditis elegans to uncover intrinsic factors that inhibit regeneration of axotomized mature neurons, opening avenues for potential therapeutics.

A DLK-dependent axon self-destruction program promotes Wallerian degeneration