Mechanism of USP18-Mediated NCOA4 m6A Modification Via Maintaining FTO Stability In Regulating Ferritinophagy-Mediated Ferroptosis in Cerebral Ischemia–Reperfusion Injury

Overexpression of USP18 in MCAO models reduced cerebral infarct size and improved brain tissue conditions.

• USP18 may regulate brain injury responses through its interaction with fat mass and obesity-associated proteins (FTO).
• Increased levels of USP18 were associated with decreased iron content, malondialdehyde (MDA), reactive oxygen species (ROS), and lactate dehydrogenase (LDH) release.
• In both MCAO models and oxygen-glucose deprivation/reperfusion (OGD/R) cells, USP18 was linked to increased cell viability and higher levels of glutathione (GSH).
• USP18 is suggested to enhance autophagy flux by promoting the expression of LC3.
• FTO and NCOA4 may counteract the protective effects of USP18 against ferroptosis in neuronal cells.
• The findings indicate that USP18 maintains FTO stability, which is involved in the suppression of NCOA4 translation and subsequent inhibition of ferroptosis.

AI simplified