Restoring cardiolipin homeostasis mitigates cerebral ischemia-reperfusion injury by suppressing ATG5-mediated neuronal autophagy-dependent ferroptosis - PubMed
5 hours ago
- #Autophagy
- #Ferroptosis
- #Cardiolipin
- Cardiolipin (CL) homeostasis is crucial in mitigating cerebral ischemia-reperfusion (I/R) injury.
- CL depletion and acyl chain remodeling occur in peri-infarct brain tissues post I/R injury.
- Extracellular vesicles (EVs) contribute to CL loss; inhibiting EV release restores neuronal CL levels.
- SS-31 peptide inhibits CL release, preserves CL content, and restores CL homeostasis.
- Restoring CL homeostasis attenuates I/R injury by suppressing neuronal ferroptosis.
- SS-31 downregulates autophagy-associated genes, with ATG5 as a key target.
- Activating autophagy or overexpressing ATG5 reverses SS-31's protective effects.
- Plasma CL levels in stroke patients correlate with 90-day functional outcomes.
- SS-31 offers a novel therapeutic avenue for stroke by targeting CL homeostasis and autophagy-dependent ferroptosis.