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Melatonin attenuates oxidative stress-induced ferroptosis of nucleus pulposus cells and intervertebral disc degeneration via PI3K/AKT-mTOR pathway - PubMed

4 hours ago
  • #melatonin
  • #IVDD
  • #ferroptosis
  • Melatonin protects nucleus pulposus cells from oxidative stress-induced ferroptosis and intervertebral disc degeneration (IVDD).
  • The study used multi-omics analyses, human NP specimens, cultured NP cells, and a rat IVDD model to evaluate melatonin's effects.
  • Melatonin restored GSH levels, reduced Fe2+ accumulation and ROS, preserved mitochondrial morphology, and upregulated SLC7A11 and GPX4.
  • It also improved ECM metabolism by increasing collagen II, aggrecan, and osteonectin while suppressing MMP-9 and ADAMTS5.
  • Protective effects were dependent on MT1/MT2 receptors and PI3K/AKT-mTOR pathway activation.
  • In vivo, melatonin reduced disc degeneration, apoptosis, and normalized ferroptosis markers.
  • Clinical and protein-level evidence suggests MT1 may be the primary therapeutic target.
  • Melatonin is a promising, low-toxicity candidate for delaying IVDD progression.