The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury
The mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults. Whether targeting this pathway is beneficial to brain injury remains unclear. In this study, we showed that adeno-associated viru...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-11-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-00113 |
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| _version_ | 1841556346447593472 |
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| author | Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang |
| author_facet | Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang |
| author_sort | Xiaoling Zhong |
| collection | DOAJ |
| description | The mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults. Whether targeting this pathway is beneficial to brain injury remains unclear. In this study, we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis, tauopathy, lesion size, and behavioral deficits. Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain. Mechanistically, the Citron homology domain acted as a dominant-negative mutant, impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway. These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury. |
| format | Article |
| id | doaj-art-42e697db29c7481e81fffa15935e6c92 |
| institution | Kabale University |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-42e697db29c7481e81fffa15935e6c922025-01-07T09:49:28ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-11-0120113233324410.4103/NRR.NRR-D-24-00113The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injuryXiaoling ZhongWenjiao TaiMeng-Lu LiuShuaipeng MaTianjin ShenYuhua ZouChun-Li ZhangThe mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults. Whether targeting this pathway is beneficial to brain injury remains unclear. In this study, we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis, tauopathy, lesion size, and behavioral deficits. Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain. Mechanistically, the Citron homology domain acted as a dominant-negative mutant, impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway. These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.https://journals.lww.com/10.4103/NRR.NRR-D-24-00113adeno-associated viruscitron homologycitron homology domaingene therapymitogen-activated protein kinase kinase kinase kinasestraumatic brain injury |
| spellingShingle | Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury Neural Regeneration Research adeno-associated virus citron homology citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury |
| title | The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury |
| title_full | The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury |
| title_fullStr | The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury |
| title_full_unstemmed | The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury |
| title_short | The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury |
| title_sort | citron homology domain of map4ks improves outcomes of traumatic brain injury |
| topic | adeno-associated virus citron homology citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-00113 |
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