Abstract
Injured axons in the adult central nervous system (CNS) exhibit almost no regeneration. Several myelin-associated proteins such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte-myelin glycoprotein (OMgp) have been identified as inhibitors of CNS axonal regeneration in the CNS. Recently, repulsive guidance molecule (RGM) was identified as a potential myelinderived neurite outgrowth inhibitor in vitro and in vivo. These axonal growth inhibitors transmit inhibitory signals through common intracellular molecules such as RhoA and its effector Rho kinases (ROCK). The effects of these axonal growth inhibitors are blocked by inhibition of the Rho-ROCK pathway in vitro. Injuries to the adult CNS induce the activation of the Rho-ROCK pathway, and the inhibition of this pathway promotes axonal regeneration and functional recovery in the injured CNS. Therefore, the Rho-ROCK pathway is a promising target for drug development for the treatment of human CNS injuries such as spinal cord injuries. This review also discusses recent patents and future developments which are useful in the treatment of human CNS injuries.
Keywords: Neuron, spinal cord, Rho, Rho-kinase, axonal regeneration, central nervous system injury
Recent Patents on CNS Drug Discovery (Discontinued)
Title: Rho-ROCK Inhibitors for the Treatment of CNS Injury
Volume: 2 Issue: 3
Author(s): Takekazu Kubo and Toshihide Yamashita
Affiliation:
Keywords: Neuron, spinal cord, Rho, Rho-kinase, axonal regeneration, central nervous system injury
Abstract: Injured axons in the adult central nervous system (CNS) exhibit almost no regeneration. Several myelin-associated proteins such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte-myelin glycoprotein (OMgp) have been identified as inhibitors of CNS axonal regeneration in the CNS. Recently, repulsive guidance molecule (RGM) was identified as a potential myelinderived neurite outgrowth inhibitor in vitro and in vivo. These axonal growth inhibitors transmit inhibitory signals through common intracellular molecules such as RhoA and its effector Rho kinases (ROCK). The effects of these axonal growth inhibitors are blocked by inhibition of the Rho-ROCK pathway in vitro. Injuries to the adult CNS induce the activation of the Rho-ROCK pathway, and the inhibition of this pathway promotes axonal regeneration and functional recovery in the injured CNS. Therefore, the Rho-ROCK pathway is a promising target for drug development for the treatment of human CNS injuries such as spinal cord injuries. This review also discusses recent patents and future developments which are useful in the treatment of human CNS injuries.
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Cite this article as:
Kubo Takekazu and Yamashita Toshihide, Rho-ROCK Inhibitors for the Treatment of CNS Injury, Recent Patents on CNS Drug Discovery (Discontinued) 2007; 2 (3) . https://dx.doi.org/10.2174/157488907782411738
DOI https://dx.doi.org/10.2174/157488907782411738 |
Print ISSN 1574-8898 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3954 |
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