Rho/ROCK Pathway and Noncoding RNAs: Implications in Ischemic Stroke and Spinal Cord Injury

Int J Mol Sci. 2021 Oct 26;22(21):11573. doi: 10.3390/ijms222111573.

Abstract

Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates a downstream effector, ROCK. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were previously considered to be non-functional. However, they have attracted much attention because they play an essential role in regulating gene expression in physiological and pathological conditions. There is growing evidence that ROCK inhibitors, such as fasudil and VX-210, can reduce injury in IS and SCI in animal models and clinical trials. Recently, it has been reported that miRNAs are decreased in IS and SCI, while lncRNAs are increased. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.

Keywords: Rho; Rho kinase; angiogenesis; apoptosis; axon regrowth; inflammation; neurogenesis; noncoding RNA; spinal cord injury; stroke.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Ischemia / genetics*
  • Brain Ischemia / pathology
  • Humans
  • Ischemic Stroke / genetics*
  • Ischemic Stroke / pathology
  • RNA, Untranslated / genetics*
  • Signal Transduction / genetics*
  • Spinal Cord / pathology
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / pathology*
  • rho-Associated Kinases / genetics*

Substances

  • RNA, Untranslated
  • rho-Associated Kinases