Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene
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Date
12/2001Author
Mack, Till GA
et al
Metadata
Abstract
Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the
C57BL/WldS mouse are protected. The degenerative and protective mechanisms are unknown. We
identified the protective gene, which encodes an N-terminal fragment of ubiquitination factor E4B
(Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), and showed that it
confers a dose-dependent block of Wallerian degeneration. Transected distal axons survived for two
weeks, and neuromuscular junctions were also protected. Surprisingly, the Wld protein was located
predominantly in the nucleus, indicating an indirect protective mechanism. Nmnat enzyme activity,
but not NAD+ content, was increased fourfold in WldS tissues. Thus, axon protection is likely to be
mediated by altered ubiquitination or pyridine nucleotide metabolism.