ADGRG1-targeted hypoxia preconditioned extracellular vesicles ameliorate intervertebral disc degeneration by delivering taurine to disrupt the oxidative stress feedback loop-driven ferroptosis in nucl
5 hours ago
- #Oxidative stress
- #Ferroptosis
- #ADGRG1
- Intervertebral disc degeneration (IVDD) causes cervical spondylosis and low back pain, leading to clinical disability.
- Excessive reactive oxygen species (ROS) drive IVDD, but mechanisms linking ROS to disc cell dysfunction remain unclear.
- A 'ROS-Mitochondrial dysfunction-Ferritinophagy' oxidative stress feedback loop is identified as central to ROS-induced nucleus pulposus cell (NPC) ferroptosis in IVDD.
- ADGRG1 is a biomarker of ROS-induced ferroptosis in injured NPCs.
- ADGRG1-tethered peptide (A1TP)-modified hypoxia preconditioned extracellular vesicles (HX-EVs) were developed for targeted antioxidant therapy.
- HX-EVs deliver taurine, which binds to LKB1 and MO25 residues, facilitating the assembly of the LKB1-STRAD-MO25 kinase complex.
- This interaction activates the AMPK/NRF2 pathway, suppressing ferritinophagy, enhancing mitochondrial repair, and protecting NPCs from ferroptosis.
- The A1TP-HX-EV system shows promise for IVDD treatment and provides insights into targeted HX-EV delivery and disc regeneration.