半乳糖凝集素-3激活酪氨酸激酶3以改善创伤性脑损伤后海马神经元的铁死亡。
Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury.
作者信息
Zhang Xiao, Li Manrui, Xu Yang, Wu Jingting, Yuan Ruixuan, Sun Yihan, Chen Xiaogang, Lv Meili, Jin Bo, Chen Xiameng, Liang Weibo
机构信息
Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, China.
Department of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, China.
出版信息
Mol Ther Nucleic Acids. 2024 Dec 21;36(1):102433. doi: 10.1016/j.omtn.2024.102433. eCollection 2025 Mar 11.
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 and studies using a controlled cortical impact (CCI) model. We observed that knockdown exacerbated ferroptosis, while overexpression mitigated it. Moreover, treatment with the agonist Gal-3 conferred protective effects, improving both motor and cognitive functions through activation. These results highlight as a promising therapeutic target for TBI.
创伤性脑损伤（TBI）会导致海马神经元大量丢失，进而导致认知功能障碍。我们对TBI后海马组织单细胞RNA测序数据进行的生物信息学分析显示，存在持续性神经元丢失以及铁死亡相关通路的激活。值得注意的是，Tyro3表达显著上调，表明其在神经元铁死亡中可能发挥作用。这一发现在用控制性皮质撞击（CCI）模型进行的[具体研究1]和[具体研究2]中均得到了进一步验证。我们观察到，[Tyro3]敲低会加剧铁死亡，而[Tyro3]过表达则会减轻铁死亡。此外，用[Gal-3]激动剂进行治疗具有保护作用，通过[相关机制]激活改善运动和认知功能。这些结果突出了[Tyro3]作为TBI一个有前景的治疗靶点。
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