What question did this study set out to answer?

This research aims to investigate how ZFP36L1 influences microglial ferroptosis in the context of ischemic stroke.

May 1, 20260 citations

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

ASAi-Xia SongHebei Medical University JHJin Han-xuHebei North University YSYuanxin SunHebei North University

Key Points

This research aims to investigate how ZFP36L1 influences microglial ferroptosis in the context of ischemic stroke.
Used OGD/R model in microglia to study ferroptosis and inflammatory responses.
Silenced ZFP36L1 to observe effects on ACSL1 and FTO.
Examined changes in m6A modification status and expression of specific mRNAs.
ZFP36L1 silencing reduced ferroptosis and inflammation in microglia, improving cerebral ischemic injury.
ACSL1 overexpression reversed the protective effects seen with ZFP36L1 silencing.
ZFP36L1 increased ACSL1 m6A modification and expression, promoting microglial ferroptosis.

Abstract

, 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.

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