Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Rho-ROCK Inhibitors as Emerging Strategies to Promote Nerve Regeneration

Author(s): Takekazu Kubo, Katsuhiko Hata, Atsushi Yamaguchi and Toshihide Yamashita

Volume 13, Issue 24, 2007

Page: [2493 - 2499] Pages: 7

DOI: 10.2174/138161207781368657

Price: $65

Abstract

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.

Keywords: Myelin, p75, Rho, repulsive guidance molecule, regeneration, central nervous system


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy