The Citron Homology Domain of MAP4Ks Improves Outcomes of Traumatic Brain Injury

Overview

Journal Neural Regen Res

Date 2024 Sep 24

PMID 39314140

Authors

Xiaoling Zhong

Wenjiao Tai

Meng-Lu Liu

Shuaipeng Ma

Tianjin Shen

Yuhua Zou

Chun-Li Zhang

Affiliations

Soon will be listed here.

Abstract

JOURNAL/nrgr/04.03/01300535-202511000-00027/figure1/v/2024-12-20T164640Z/r/image-tiff 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.

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