An unbiased transcriptional profiling screen reveals the secreted matrix metalloproteinase MMP-1 is a transcriptional target of the ensheathing glial receptor Draper following acute axon injury in adult Drosophila.
Two seemingly distinct cellular stress response pathways that contribute to neurodegeneration after axonal insults are now revealed to be under the control of a single master regulator of the neuronal injury response, the kinase DLK.
Synaptic defects previously attributed to loss of kinesin function are found to be mediated by the Wnd/DLK axonal injury signaling pathway, which restrains the total levels of presynaptic proteins in response to their accumulation.
Axonal metabolic flux analysis demonstrates that expression of NMNAT1 blocks axonal degeneration in cultured mouse neurons not by altering NAD+ synthesis, but rather by inhibiting injury-induced, SARM1-dependent NAD+ consumption.
A function-based genetic screen using the Caenorhabditis elegans axotomy model identifies new regulators and an inhibitory role for NAD+ in axon regeneration, expanding the understanding of axon injury responses and regeneration.
Defects in synapse regeneration limit functional circuit recovery after nerve injury by misdirecting information via ectopic dendritic synapses, and also by functional and molecular deficits in reformed axonal synapses.