Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene
Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene
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DOI：
10.1038/nn770
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发表时间：
2001-12-01
影响因子：
25
通讯作者：
Coleman, MP
中科院分区：
文献类型：
--
作者：
Mack, TGA;Reiner, M;Coleman, MP
损伤远端的轴突及其突触会经历快速的沃勒变性，但C57 BL/Wld（S）小鼠的轴突受到保护。退化和保护机制尚不清楚。我们确定了保护基因，它编码的N-末端片段的泛素化因子E4 B（Ube 4 b）融合到烟酰胺单核苷酸腺苷酸转移酶（Nmnat），并表明它赋予了剂量依赖性块沃勒变性。横断的远端轴突存活两周，神经肌肉接头也受到保护。令人惊讶的是，Wld蛋白主要位于细胞核中，表明间接保护机制。在Wld（S）组织中，Nmnat酶活性增加了4倍，但NAD（+）含量没有增加。因此，轴突保护很可能是通过改变泛素化或吡啶核苷酸代谢介导的。
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.