A CREB5-NR4A1 checkpoint protects against disc degeneration by controlling ferroptosis - PubMed
5 hours ago
- #disc degeneration
- #CREB5-NR4A1
- #ferroptosis
- CREB5-NR4A1 checkpoint protects against intervertebral disc degeneration (IDD) by controlling ferroptosis.
- CREB5 expression is significantly reduced in human degenerative discs.
- CREB5 overexpression restores anti-ferroptotic enzyme GPX4 and suppresses ACSL4 induction in oxidatively stressed nucleus pulposus (NP) cells.
- CREB5 activates NR4A1, promoting NR4A1-dependent transcription of PGC-1α and restoring mitochondrial antioxidant capacity.
- In vivo, CREB5 delivery preserves disc height and reduces lipid peroxidation.
- CREB5 functions as a transcriptional checkpoint limiting ferroptosis via the NR4A1-PGC-1α axis.