Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene

Mack, TGA; Reiner, M; Beirowski, B; Mi, WQ; Emanuelli, M; Wagner, D.; Thomson, D; Gillingwater, T; Court, F; Conforti, L; Fernando, FS; Tarlton, A; Andressen, C; Addicks, K; Magni, G; et. al.


Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the C57BL/Wld(S) 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 Wld(S) tissues. Thus, axon protection is likely to be mediated by altered ubiquitination or pyridine nucleotide metabolism.

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Título según WOS: ID WOS:000172525000016 Not found in local WOS DB
Título de la Revista: NATURE NEUROSCIENCE
Volumen: 4
Número: 12
Fecha de publicación: 2001
Página de inicio: 1199
Página final: 1206


Notas: ISI