Rho-ROCK inhibitors as emerging strategies to promote nerve regeneration.
Rho-ROCK inhibitors as emerging strategies to promote nerve regeneration.
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DOI：
10.2174/138161207781368657
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发表时间：
2007-07
影响因子：
3.1
通讯作者：
T. Kubo;K. Hata;A. Yamaguchi;T. Yamashita
中科院分区：
文献类型：
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作者：
T. Kubo;K. Hata;A. Yamaguchi;T. Yamashita
中枢神经系统（CNS）中的几种髓鞘相关蛋白已被鉴定为成年脊椎动物CNS损伤后轴突再生的抑制剂。在这些抑制剂中，髓鞘相关糖蛋白（MAG），Nogo和少突胶质细胞髓鞘糖蛋白（OMgp）的特点。最近，排斥导向分子（RGM）被认为是一种有效的髓鞘衍生的神经突起生长抑制剂在体外和体内。这些抑制剂的受体和下游信号的发现使得能够进一步理解轴突再生失败的机制。RhoA及其效应物Rho激酶（ROCK）在这些抑制剂与相应的受体连接后的激活已被证明是轴突生长抑制的关键因素。Rho-ROCK通路的阻断可以逆转这些抑制剂在体外的抑制作用，并促进体内轴突再生。因此，Rho-ROCK抑制剂具有针对人CNS损伤（例如脊髓损伤）的治疗潜力。
Several myelin-associated proteins in the central nervous system (CNS) have been identified as inhibitors of axonal regeneration following the injury of the adult vertebrate CNS. Among these inhibitors, myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte-myelin glycoprotein (OMgp) are well characterized. Recently, the repulsive guidance molecule (RGM) was included as a potent myelin-derived neurite outgrowth inhibitor in vitro and in vivo. The discovery of the receptors and downstream signals of these inhibitors enabled further understanding of the mechanism underlying the failure of axonal regeneration. The activation of RhoA and its effector Rho kinases (ROCK) after the ligation of these inhibitors to the corresponding receptors has been shown to be a key element for axonal growth inhibition. Blockade of the Rho-ROCK pathway reverses the inhibitory effects of these inhibitors in vitro and promotes axonal regeneration in vivo. Therefore, the Rho-ROCK inhibitors have a therapeutic potential against injuries to the human CNS, such as spinal cord injuries.