Wallerian axonal degeneration? Not in C. elegans!

Injury-induced neuronal damage is often followed by Wallerian Degeneration (WD). WD, named for the British physician Augustus Waller, is characterized by the loss of axons in the injured region. At the molecular level, WD is promoted when the transport of the enzyme NMNAT2 to the axonal region is harmed. This causes an accumulation of the metabolite NMN, which is normally consumed by NMNAT2, and activation of the pro-degenerative NADase SARM1. Inhibition of SARM1, even in the absence of NMNAT2, prevents WD. Multiple models, including flies, zebrafish, mice and humans, exhibit WD. Interestingly, this is not the case in the nematode C. elegans. In a study published in Nature Communications, Prof. Yarden Opatowsky and his team used a crystallographic approach to compare the human SARM1 and the C. elegans ortholog TIR-1. The activity of TIR-1 was found to be considerably weaker. Moreover, expression of the human SARM1 in the nematodes resulted in an injury-induced WD.