Resveratrol Upregulates miR-124-3p Expression to Target DAPK1, Regulating the NLRP3/Caspase-1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury

Spinal cord injury (SCI) has limited effective treatments, making the prevention of secondary injury crucial. Pyroptosis, a form of cell death, worsens SCI during the secondary injury phase; therefore, inhibiting pyroptosis could aid recovery. This study explores how resveratrol (RES), a natural compound, and miR-124-3p, a small RNA molecule, might work to reduce pyroptosis and promote spinal cord repair, potentially offering new clinical treatments for SCI. The research demonstrated that RES increases miR-124-3p levels, which in turn targets DAPK1 (a protein involved in cell death), thereby regulating the NLRP3/Caspase-1/GSDMD pathway. This regulation inhibits pyroptosis and aids in alleviating SCI.

• 1
  DAPK1 interacts with NLRP3, promoting pyroptosis via the NLRP3/Caspase-1/GSDMD pathway. Knocking down DAPK1 inhibits pyroptosis.
• 2
  miR-124-3p negatively regulates DAPK1 levels, reducing cell pyroptosis. RES increases miR-124-3p expression and reduces DAPK1 expression, impacting the NLRP3/Caspase-1/GSDMD pathway and inhibiting pyroptosis.
• 3
  In vivo, RES reduces GSDMD-N levels in rats with SCI, promoting functional recovery from SCI. RES increases miR-124-3p, targets DAPK1, regulates the NLRP3/Caspase-1/GSDMD pathway, inhibits pyroptosis, and alleviates SCI.