1. Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury
- Author
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Xiao Zhang, Manrui Li, Yang Xu, Jingting Wu, Ruixuan Yuan, Yihan Sun, Xiaogang Chen, Meili Lv, Bo Jin, Xiameng Chen, and Weibo Liang
- Subjects
MT: Bioinformatics ,traumatic brain injury ,hippocampal neuron ,ferroptosis ,Tyro3 ,Gal-3 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Traumatic brain injury (TBI) leads to significant hippocampal neuronal loss, contributing to cognitive dysfunction. Our bioinformatics analysis of single-cell RNA sequencing data from hippocampal tissue following TBI revealed persistent neuronal loss and activation of ferroptosis-related pathways. Notably, Tyro3 expression was significantly upregulated, suggesting its potential role in neuronal ferroptosis. This finding was further validated in both in vivo and in vitro studies using a controlled cortical impact (CCI) model. We observed that Tyro3 knockdown exacerbated ferroptosis, while Tyro3 overexpression mitigated it. Moreover, treatment with the Tyro3 agonist Gal-3 conferred protective effects, improving both motor and cognitive functions through Tyro3 activation. These results highlight Tyro3 as a promising therapeutic target for TBI.
- Published
- 2025
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