The therapeutic effects of Rho-ROCK inhibitors on CNS disorders

The Rho-ROCK pathway is a signaling system involved in many neuronal functions, including the growth and retraction of neurites (nerve fibers). Because of its connection to the development of several central nervous system (CNS) disorders, like spinal cord injuries, stroke, and Alzheimer’s disease, it is becoming an attractive target for drug development. In the adult CNS, axons do not regenerate well after injury due to the presence of myelin-associated axonal growth inhibitors. However, blocking the Rho-ROCK pathway can reverse the effects of these inhibitors, promoting axonal regeneration and functional recovery. Rho-ROCK inhibitors have shown therapeutic effects in animal models of stroke, suggesting their potential for treating human CNS disorders.

• 1
  Inhibition of the Rho-ROCK pathway reverses the effects of myelin-associated inhibitors, promoting axonal regeneration and functional recovery in the injured CNS in vivo.
• 2
  Rho-ROCK inhibitors have shown therapeutic effects in animal models of stroke, partly mediated by upregulated expression of endothelial NO synthase and increased cerebral blood flow.
• 3
  In Alzheimer's disease models, statins inhibit small GTPases including Rho, leading to activation of α-secretase cleavage or enhancement of APP lysosomal degradation, both of which inhibit Aβ production.