ZFP36L1 Enhances Microglial Ferroptosis in Ischemic Stroke by Reducing FTO-Mediated N6-Methyladenosine Demethylation of ACSL1 mRNA.

, lipid peroxidation, inflammatory factors, along with an increased Glutathione/Glutathione disulfide ratio. Additionally, ZFP36L1 silencing suppressed the OGD/R-induced promotion of ferroptosis and inflammation in microglia and alleviated cerebral ischemic injury in MCAO/R mice, whereas ACSL1 overexpression reversed these alterations caused by ZFP36L1 silencing. Mechanistically, ZFP36L1 decreased FTO messenger RNA (mRNA) stability and reduced FTO expression. FTO overexpression reduced ACSL1 N6-methyladenosine (m6A) modification and ACSL1 expression. In conclusion, ZFP36L1 increased ACSL1 m6A modification and ACSL1 expression to promote microglial ferroptosis, neuroinflammatory response, and cerebral ischemic injury in IS by reducing FTO mRNA stability.