MicroRNA-based therapeutics in central nervous system injuries

J Cereb Blood Flow Metab. 2018 Jul;38(7):1125-1148. doi: 10.1177/0271678X18773871. Epub 2018 Apr 30.

Abstract

Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.

Keywords: MicroRNA mimics; microRNA inhibitors; spinal cord injury; stroke; traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain Injuries, Traumatic / metabolism
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / therapy*
  • Drug Delivery Systems / methods*
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / therapy
  • MicroRNAs / therapeutic use*
  • Oxidative Stress / drug effects
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / therapy*
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / therapy*

Substances

  • MicroRNAs