Wallerian Degeneration Involves Rho/Rho-kinase Signaling*
Wallerian Degeneration Involves Rho/Rho-kinase Signaling*
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DOI：
10.1074/jbc.m501945200
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发表时间：
2005-05
影响因子：
4.8
通讯作者：
S. Yamagishi;M. Fujitani;K. Hata;Keiko Kitajo;Fumiaki Mimura;H. Abe;T. Yamashita
中科院分区：
文献类型：
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作者：
S. Yamagishi;M. Fujitani;K. Hata;Keiko Kitajo;Fumiaki Mimura;H. Abe;T. Yamashita
局部轴突变性是许多神经退行性疾病的共同病理特征，而其潜在的分子机制在很大程度上是未知的。在这项研究中，我们使用被称为“沃勒氏变性”的横断轴突变性作为模型来检查Rho的可能参与。髓磷脂来源的轴突再生抑制剂Nogo-66在体外显著加速了背根神经节外植体的轴突退化，而抑制rho激酶活性则消除了这一作用。脊髓损伤后，在损伤轴突远端观察到Rho活化。我们证明，在体内，rho激酶抑制剂显著延缓了受损皮质-脊髓轴突的退化。我们的研究结果表明，在病理条件下，抑制信号通路可能会延缓轴突退化。
Local axon degeneration is a common pathological feature of many neurodegenerative diseases, whereas the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed “Wallerian degeneration,” as a model to examine the possible involvement of Rho. Nogo-66, a myelin-derived inhibitor of axon regeneration, significantly accelerated axon degeneration of the dorsal root ganglion explant in vitro, whereas inhibiting Rho-kinase activity abolished the effect. Rho activation was observed in the distal part of the injured axons after spinal cord injury. We demonstrate that degeneration of the injured cortico-spinal axons was significantly retarded by a Rho-kinase inhibitor in vivo. Our findings suggest that inhibiting the signaling pathway may retard axon degeneration in pathological conditions.