Axon growth inhibition by RhoA/ROCK in the central nervous system.
Axon growth inhibition by RhoA/ROCK in the central nervous system.
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DOI：
10.3389/fnins.2014.00338
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发表时间：
2014
影响因子：
4.3
通讯作者：
Yamashita T
中科院分区：
文献类型：
--
作者：
Fujita Y;Yamashita T
Rho激酶（ROCK）是一种丝氨酸/苏氨酸激酶，是小GTdR Rho的下游靶标。RhoA/ROCK通路与各种神经元功能如迁移、树突发育和轴突延伸相关。来自动物研究的证据表明，RhoA/ROCK信号转导参与各种中枢神经系统（CNS）疾病，包括视神经和脊髓损伤、中风和神经退行性疾病。鉴于RhoA/ROCK在CNS疾病的病理生理学中起关键作用，预期靶向该途径的治疗剂的开发将有助于CNS疾病的治疗。RhoA/ROCK通路介导髓鞘相关轴突生长因子-Nogo、髓鞘相关糖蛋白（MAG）、少突胶质细胞髓鞘糖蛋白（OMgp）和排斥导向分子（RGM）的作用。阻断RhoA/ROCK信号通路可以逆转这些分子对轴突生长的抑制作用，并促进CNS损伤动物模型中的轴突发芽和功能恢复。迄今为止，几种RhoA/ROCK抑制剂已经在开发中或在临床试验中作为神经系统疾病的治疗剂。本文就RhoA/ROCK信号通路在神经系统疾病中的作用作一综述。我们还讨论了RhoA/ROCK抑制剂对各种神经系统疾病的潜在治疗方法。
Rho kinase (ROCK) is a serine/threonine kinase and a downstream target of the small GTPase Rho. The RhoA/ROCK pathway is associated with various neuronal functions such as migration, dendrite development, and axonal extension. Evidence from animal studies reveals that RhoA/ROCK signaling is involved in various central nervous system (CNS) diseases, including optic nerve and spinal cord injuries, stroke, and neurodegenerative diseases. Given that RhoA/ROCK plays a critical role in the pathophysiology of CNS diseases, the development of therapeutic agents targeting this pathway is expected to contribute to the treatment of CNS diseases. The RhoA/ROCK pathway mediates the effects of myelin-associated axon growth inhibitors—Nogo, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and repulsive guidance molecule (RGM). Blocking RhoA/ROCK signaling can reverse the inhibitory effects of these molecules on axon outgrowth, and promotes axonal sprouting and functional recovery in animal models of CNS injury. To date, several RhoA/ROCK inhibitors have been under development or in clinical trials as therapeutic agents for neurological disorders. In this review, we focus on the RhoA/ROCK signaling pathway in neurological disorders. We also discuss the potential therapeutic approaches of RhoA/ROCK inhibitors for various neurological disorders.
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影响因子：
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作者：
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