The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury  

作　　者：Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang 

机构地区：[1]Department of Molecular Biology,University of Texas Southwestern Medical Center,Dallas,TX,USA [2]Hamon Center for Regenerative Science and Medicine,University of Texas Southwestern Medical Center,Dallas,TX,USA [3]Peter O’Donnell Jr.Brain Institute,University of Texas Southwestern Medical Center,Dallas,TX,USA

出　　处：《Neural Regeneration Research》2025年第11期3233-3244,共12页中国神经再生研究（英文版）

基　　金：supported by the TARCC,Welch Foundation Award(I-1724);the Decherd Foundation;the Pape Adams Foundation,NIH grants NS092616,NS127375,NS117065,NS111776。

摘　　要：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.

关 键 词：adeno-associated virus Citron homology Citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury 

分 类 号：R651.15[医药卫生—外科学]