Rho-ROCK inhibitors as emerging strategies to promote nerve regeneration.
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.
Kubo
Takekazu
T
Department of Neurobiology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan. kubo@restaff.chiba-u.jp
Hata
Katsuhiko
K
Yamaguchi
Atsushi
A
Yamashita
Toshihide
T
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases