What question did this study set out to answer?

The research aims to delineate the role of STIM1 in neuronal injury following intracerebral hemorrhage by studying its effects on ferroptosis and iron homeostasis.

February 14, 2026Open Access

The Ca2+ sensor STIM1 promotes neuronal ferroptosis by regulating iron homeostasis to exacerbate brain injury after intracerebral hemorrhage

Key Points

The research aims to delineate the role of STIM1 in neuronal injury following intracerebral hemorrhage by studying its effects on ferroptosis and iron homeostasis.
Analyzed STIM1 levels in neurons after intracerebral hemorrhage in mice.
Measured plasma STIM1 levels in patients to assess correlation with prognosis.
Conducted knockout experiments to determine the impact of STIM1 absence on brain injury.
Used virtual screening to identify S-IN-1 as an inhibitor of STIM1-TFR1 interaction.
Elevated STIM1 levels were found in neurons and plasma in ICH patients, correlating with poor outcomes.
Knocking out STIM1 in mice resulted in reduced brain tissue damage and improved neurological function.
STIM1 was shown to promote ferroptosis by regulating iron homeostasis through TFR1 interaction.
S-IN-1 effectively protected against neuronal ferroptosis and brain injury by targeting STIM1.

Abstract

Intracerebral hemorrhage (ICH) often has a poor prognosis, necessitating the exploration of effective therapeutic targets. Stromal interaction molecule 1 (STIM1) is a crucial regulator of cellular calcium homeostasis, but its specific role in ICH remains unclear. This study finds consistent elevation of STIM1 in neurons after ICH, with increased plasma levels in patients correlating with poor prognosis. Neuronal knockout of STIM1 in mice improves brain tissue damage and neurological injury. Mechanistically, STIM1 exacerbates neuronal injury primarily by promoting ferroptosis. Importantly, in addition to regulating calcium signaling pathways, STIM1 directly regulates iron homeostasis through its interaction with transferrin receptor 1 (TFR1) to promote ferroptosis. Finally, through virtual screening, S-IN-1 is identified as an inhibitor targeting STIM1-TFR1 interaction, protecting against neuronal ferroptosis and brain injury. These findings confirm the molecular function of STIM1 in regulating iron homeostasis, providing valuable insights and promising targets for ICH treatment.

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Cite This Study

Zhang et al. (Sun,) studied this question.

synapsesocial.com/papers/699010382ccff479cfe56cbd https://doi.org/https://doi.org/10.1016/j.xcrm.2026.102595

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