TGR5 activation shields mitochondria and limits AIM2 pyroptosis after spinal cord injury
- TGR5 expression rose after contusion injury in mice and in stressed microglia, and the agonist INT-777 improved functional recovery and tissue repair.
- Activation worked through cAMP/AMPK signalling to preserve mitochondrial function and curb mtDNA release, which in turn dampened AIM2-driven pyroptosis and inflammation.
- Forcing AIM2 expression partly reversed the benefit, supporting the proposed pathway.
💡 Points Based on the abstract
INT-777 is a tool compound with poor drug-like properties, and the dosing window after injury is the real clinical question: spinal cord trials fail when treatment starts hours late. I'd want a delayed-dosing arm and CNS exposure data before believing TGR5 is the lever. Also, TGR5 agonists carry gallbladder and itch liabilities that a short acute-injury course may sidestep.