Acute Pharmacological Inhibition of Protein Kinase R-Like Endoplasmic Reticulum Kinase Signaling After Spinal Cord Injury Spares Oligodendrocytes and Improves Locomotor Recovery

This study investigates the role of PERK, a protein involved in cellular stress response, after spinal cord injury (SCI) in mice. The researchers found that inhibiting PERK shortly after SCI improved the recovery of movement and reduced damage to white matter in the spinal cord. The study suggests that excessive activation of PERK after SCI contributes to white matter damage. The scientists observed increased numbers of oligodendrocytes, cells critical for nerve insulation, in mice treated with a PERK inhibitor called GSK2656157. In laboratory experiments, GSK2656157 protected oligodendrocyte precursor cells from stress-induced damage. This suggests that targeting PERK could be a potential therapeutic strategy to protect the central nervous system after acute injuries like SCI.

• 1
  Acute inhibition of PERK with GSK2656157 after SCI reduced ER stress, improved white matter sparing, and enhanced hindlimb locomotion recovery in mice.
• 2
  GSK2656157 treatment increased the number of oligodendrocytes at the injury epicenter, suggesting a protective effect on these cells.
• 3
  In vitro, GSK2656157 protected primary mouse oligodendrocyte precursor cells from ER stress-induced cytotoxicity.