Genetic protection from axon injury

Axons and their synapses distal to the site of an injury undergo rapid degeneration, but axons in the mutant C57BL/Wld^S mouse are protected by a mechanism that remains unclear. In December Nature Neuroscience Till Mack and colleagues from University of Cologne, Germany, identified the Wld gene and the mutant protein involved in protecting the nerve fibers of these mice from degeneration.

Mack et al. found that the protection in C57BL/Wld^S mice is due to a Ube4b/Nmnat chimeric gene that encodes an N-terminal fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat). The Wld protein had Nmnat enzyme activity and was detected in neuron nuclei but not in axons or Schwann cells, suggesting the existence of down-stream factors that mediate the protective effect (Nat Neurosci 2001, DOI: 10.1038/nn770).

These results offer novel therapeutic possibilities through the use of the...