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SOD1 lactylation impair its enzymatic activity by conformational change to aggravate intervertebral disc degeneration - PubMed

5 hours ago
  • #IVDD
  • #SOD1 lactylation
  • #ZL-01
  • Lactate accumulation is a hallmark of intervertebral disc degeneration (IVDD).
  • SOD1 lactylation at lysine 123 (SOD1K123la) is identified as crucial for IVDD aggravation.
  • SOD1K123la alters SOD1 conformation, impairs its enzymatic activity, and induces oxidative damage.
  • SOD1K123la activates the p53 pathway in nucleus pulposus cells (NPCs).
  • A small molecule ZL-01 inhibits SOD1K123la and alleviates IVDD in male rats.
  • NPC-targeted delivery of ZL-01 via collagen type II-targeted peptide-modified extracellular vesicles shows therapeutic potential.