Kubo Takekazu, Hata Katsuhiko, Yamaguchi Atsushi, Yamashita Toshihide
Department of Neurobiology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Curr Pharm Des. 2007;13(24):2493-9. doi: 10.2174/138161207781368657.
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.
在成年脊椎动物中枢神经系统（CNS）损伤后，几种中枢神经系统中的髓磷脂相关蛋白已被确定为轴突再生的抑制剂。在这些抑制剂中，髓磷脂相关糖蛋白（MAG）、Nogo和少突胶质细胞髓磷脂糖蛋白（OMgp）的特征已得到充分研究。最近，排斥导向分子（RGM）被列为一种在体外和体内均有效的髓磷脂衍生的神经突生长抑制剂。这些抑制剂的受体和下游信号的发现，使人们能够进一步了解轴突再生失败的潜在机制。这些抑制剂与相应受体结合后，RhoA及其效应物Rho激酶（ROCK）的激活已被证明是轴突生长抑制的关键因素。阻断Rho-ROCK途径可在体外逆转这些抑制剂的抑制作用，并在体内促进轴突再生。因此，Rho-ROCK抑制剂对人类中枢神经系统损伤，如脊髓损伤，具有治疗潜力。
