Rho-ROCK Inhibitors for the Treatment of CNS Injury

Author(s): Takekazu Kubo, Toshihide Yamashita

Journal Name: Recent Patents on CNS Drug Discovery (Discontinued)

Volume 2 , Issue 3 , 2007


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

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Article Details

Year: 2007
Page: [173 - 179]
Pages: 7
DOI: 10.2174/157488907782411738
Price: $58

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