Rho kinase, a promising drug target for neurological disorders

Nat Rev Drug Discov. 2005 May;4(5):387-98. doi: 10.1038/nrd1719.

Abstract

Rho kinases (ROCKs), the first Rho effectors to be described, are serine/threonine kinases that are important in fundamental processes of cell migration, cell proliferation and cell survival. Abnormal activation of the Rho/ROCK pathway has been observed in various disorders of the central nervous system. Injury to the adult vertebrate brain and spinal cord activates ROCKs, thereby inhibiting neurite growth and sprouting. Inhibition of ROCKs results in accelerated regeneration and enhanced functional recovery after spinal-cord injury in mammals, and inhibition of the Rho/ROCK pathway has also proved to be efficacious in animal models of stroke, inflammatory and demyelinating diseases, Alzheimer's disease and neuropathic pain. ROCK inhibitors therefore have potential for preventing neurodegeneration and stimulating neuroregeneration in various neurological disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / enzymology*
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • rho-Associated Kinases

Substances

  • Intracellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases