ROCK as a therapeutic target for ischemic stroke

Expert Rev Neurother. 2017 Dec;17(12):1167-1177. doi: 10.1080/14737175.2017.1395700. Epub 2017 Oct 30.

Abstract

Stroke is a major cause of disability and the fifth leading cause of death. Currently, the only approved acute medical treatment of ischemic stroke is tissue plasminogen activator (tPA), but its effectiveness is greatly predicated upon early administration of the drug. There is, therefore, an urgent need to find new therapeutic options for acute stroke. Areas covered: In this review, we summarize the role of Rho-associated coiled-coil containing kinase (ROCK) and its potential as a therapeutic target in stroke pathophysiology. ROCK is a major regulator of cell contractility, motility, and proliferation. Many of these ROCK-mediated processes in endothelial cells, vascular smooth muscle cells, pericytes, astrocytes, glia, neurons, leukocytes, and platelets are important in stroke pathophysiology, and the inhibition of such processes could improve stroke outcome. Expert commentary: ROCK is a potential therapeutic target for cardiovascular disease and ROCK inhibitors have already been approved for human use in Japan and China for the treatment of acute stroke. Further studies are needed to determine the role of ROCK isoforms in the pathophysiology of cerebral ischemia and whether there are further therapeutic benefits with selective ROCK inhibitors.

Keywords: Cerebral ischemia; RhoA/Rho-associated coiled-coil containing kinase (ROCK); ischemic stroke; therapeutic target.

Publication types

  • Review

MeSH terms

  • Brain Ischemia / drug therapy*
  • Humans
  • Protein Kinase Inhibitors / therapeutic use*
  • Stroke / drug therapy*
  • rho-Associated Kinases / antagonists & inhibitors*

Substances

  • Protein Kinase Inhibitors
  • rho-Associated Kinases