Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury
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. N...
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124003202 |
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| author | Xiao Zhang Manrui Li Yang Xu Jingting Wu Ruixuan Yuan Yihan Sun Xiaogang Chen Meili Lv Bo Jin Xiameng Chen Weibo Liang |
| author_facet | Xiao Zhang Manrui Li Yang Xu Jingting Wu Ruixuan Yuan Yihan Sun Xiaogang Chen Meili Lv Bo Jin Xiameng Chen Weibo Liang |
| author_sort | Xiao Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6c531e770a624e7e8908a12786241052 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-6c531e770a624e7e8908a127862410522025-01-22T05:41:43ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102433Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injuryXiao Zhang0Manrui Li1Yang Xu2Jingting Wu3Ruixuan Yuan4Yihan Sun5Xiaogang Chen6Meili Lv7Bo Jin8Xiameng Chen9Weibo Liang10Institute 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, ChinaDepartment of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, ChinaDepartment of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, ChinaDepartment of Forensic Pathology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, ChinaDepartment of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, ChinaDepartment of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, ChinaDepartment of Forensic Pathology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, ChinaDepartment of Immunology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, ChinaInstitute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, China; Corresponding author: Bo Jin, Professor, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, China.Department of Forensic Pathology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, China; Corresponding author: Xiameng Chen, Associate Professor, Department of Forensic Pathology and Forensic Clinical Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.Department of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610000, China; Corresponding author: Weibo Liang, Professor, Vice President, Department of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.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.http://www.sciencedirect.com/science/article/pii/S2162253124003202MT: Bioinformaticstraumatic brain injuryhippocampal neuronferroptosisTyro3Gal-3 |
| spellingShingle | Xiao Zhang Manrui Li Yang Xu Jingting Wu Ruixuan Yuan Yihan Sun Xiaogang Chen Meili Lv Bo Jin Xiameng Chen Weibo Liang Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury Molecular Therapy: Nucleic Acids MT: Bioinformatics traumatic brain injury hippocampal neuron ferroptosis Tyro3 Gal-3 |
| title | Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury |
| title_full | Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury |
| title_fullStr | Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury |
| title_full_unstemmed | Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury |
| title_short | Gal-3 activates Tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury |
| title_sort | gal 3 activates tyro3 to ameliorate ferroptosis of hippocampal neurons after traumatic brain injury |
| topic | MT: Bioinformatics traumatic brain injury hippocampal neuron ferroptosis Tyro3 Gal-3 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124003202 |
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