Tracking in the WIds -: The hunting of the SIRT and the luring of the draper

Wallerian degeneration of distal axons after nerve injury is significantly delayed in the Wids mutant mouse. The Wids protein is a fusion of nicotinamide mononucleotide adenyltransferase-1 (Nmnat1), an essential enzyme in the biosynthesis pathway of nicotinamide adenine dinuclecitide (NAD), with the N-terminal 70 amino acids of the Ube4b ubiquitination assembly factor. The mechanism of Wld(s) action is still enigmatic, although recent efforts suggest that it is indirect and requires sequences flanking or linking the two fused open reading frames. Three papers in this issue of Neuron now show that Wids action is conserved in Drosophila and that a critical role of Wids may be the suppression of axonal self-destruct signals that induce Draper-mediated clearance of damaged axons by glial cells.