Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Inhibition of Rho/Rho-Kinase as Therapeutic Strategy to Promote CNS Axonal Regeneration

Author(s): Mitsuharu Endo, Toshihide Yamashita.

Abstract:

After injury to the central nervous system (CNS) of adult vertebrates, axonal regeneration is extremely limited because inhibitory proteins existing around the injury site prevent the regrowth of the lesioned axons. Previous studies have reported that several myelin-derived proteins (such as Nogo, MAG, OMgp) and developmental guidance proteins (such as RGM, semaphorin, ephrin) contribute to the inhibition of axonal regeneration after injury in the adult CNS. Although each neurite growth inhibitory protein induces neurite retraction and growth cone collapse through specific receptors, they commonly utilize the function of small GTPases, including Rho, Rac, Cdc42, and Ras, that regulate neurite outgrowth by controlling actin and microtubule cytoskeleton. The small GTPase Rho and its effector Rho-kinase play critical roles in the induction of neurite retraction and growth cone collapse in vitro and the inhibition of axonal regeneration in vivo. Therefore, the Rho inhibitor C3 transferase and Rho-kinase inhibitors are thought to be effective therapeutic candidates involved in the promotion of axonal regeneration after human CNS injuries such as spinal cord injury.

Keywords: Small GTPase, Rho, Rho-kinase, actin, microtubule, CNS injury, axonal regeneration

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Article Details

VOLUME: 7
ISSUE: 4
Year: 2007
Page: [241 - 250]
Pages: 10
DOI: 10.2174/187152407783220788
Price: $58