Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS

Injuries to the central nervous system (CNS) often result in limited axon regeneration due to the presence of inhibitory molecules. This study focuses on the role of Rho GTPases, which regulate actin rearrangements in growth cones, in this inhibition. The researchers found that Nogo-66, a myelin-associated inhibitor, directly activates Rho. By inhibiting Rho or its downstream effector ROCK, they aimed to promote neurite outgrowth and axonal regeneration. The study demonstrates that inhibiting ROCK with Y-27632 enhances sprouting of corticospinal tract (CST) fibers in vivo and accelerates locomotor recovery after CST lesions in adult rats, suggesting a potential therapeutic strategy for spinal cord injuries.

• 1
  Nogo-66 directly activates Rho, as demonstrated by increased levels of GTP Rho in PC12 and DRG cell lysates after Nogo-66 stimulation.
• 2
  Inhibition of p160ROCK with Y-27632 promotes DRG outgrowth on inhibitory substrates in vitro.
• 3
  Y-27632 enhances sprouting of CST fibers in vivo and accelerates locomotor recovery after CST lesions in adult rats.