Tan Hai-Bo, Zhong Yi-Sheng, Cheng Yu, Shen Xi
Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai 200025, China.
Int J Ophthalmol. 2011;4(6):652-7. doi: 10.3980/j.issn.2222-3959.2011.06.16. Epub 2011 Dec 18.
Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway in vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cells was also discussed.
Rho相关激酶(ROCK)是一种丝氨酸/苏氨酸激酶,也是小GTP酶RhoA的主要下游效应器之一。Rho/ROCK信号通路与多种中枢神经系统(CNS)疾病的发病机制密切相关,并参与神经元功能的许多方面,包括神经突的生长和回缩。在成体中枢神经系统中,由于存在髓鞘相关轴突生长抑制剂,如Nogo、髓鞘相关糖蛋白(MAG)和少突胶质细胞-髓鞘糖蛋白(Omgp)等,受损神经元的再生非常困难。在体外,通过阻断Rho/ROCK信号通路可逆转这些轴突生长抑制剂的作用,并且在体内抑制Rho/ROCK信号通路可促进受损中枢神经系统中的轴突再生和功能恢复。此外,Rho/ROCK抑制剂的治疗效果在一些动物模型中也得到了证实,Rho/ROCK信号通路成为治疗中枢神经系统疾病药物开发的一个有吸引力的靶点。在这篇综述中,我们总结了Rho及其下游因子ROCK在神经再生中的作用,并讨论了Rho/ROCK抑制剂对视网膜神经节细胞存活和轴突再生的潜在治疗作用。