Axon growth inhibition by RhoA/ROCK in the central nervous system

被引：221

作者：

Fujita, Yuki ^{[1
,2
]}

Yamashita, Toshihide ^{[1
,2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Mol Neurosci, Suita, Osaka 5650871, Japan

[2] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo, Japan

来源：

FRONTIERS IN NEUROSCIENCE | 2014年 / 8卷

基金：

日本科学技术振兴机构;

关键词：

RhoA; ROCK; myelin; axon regeneration; central nervous system; MYELIN-ASSOCIATED GLYCOPROTEIN; SPINAL-CORD-INJURY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHONDROITIN SULFATE PROTEOGLYCANS; RHO-KINASE INHIBITOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TARGET GAMMA-SECRETASE; RETINAL GANGLION-CELLS; NOGO RECEPTOR; NEURITE OUTGROWTH;

D O I：

10.3389/fnins.2014.00338

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 (0Mgp), 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.

引用

页数：12

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