Role of Tropomodulins in brain physiology and pathology

Actin dynamics are crucial for the morphogenesis and function of neurons in the brain. Tropomodulins (Tmods) belong to a family of actin-binding proteins that cap the pointed-end of actin filaments. There are four Tmod isoforms, and three of which, Tmod1, Tmod2 and Tmod3, are expressed in the brain,...

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Main Authors: Chuan Hong, Xiaopeng Liu, Zhou Zhou, Yuan Xing, Zixuan Cao, Yan-Zhong Chang, Guofen Gao
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125002220
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author Chuan Hong
Xiaopeng Liu
Zhou Zhou
Yuan Xing
Zixuan Cao
Yan-Zhong Chang
Guofen Gao
author_facet Chuan Hong
Xiaopeng Liu
Zhou Zhou
Yuan Xing
Zixuan Cao
Yan-Zhong Chang
Guofen Gao
author_sort Chuan Hong
collection DOAJ
description Actin dynamics are crucial for the morphogenesis and function of neurons in the brain. Tropomodulins (Tmods) belong to a family of actin-binding proteins that cap the pointed-end of actin filaments. There are four Tmod isoforms, and three of which, Tmod1, Tmod2 and Tmod3, are expressed in the brain, with Tmod2 exhibiting neuronal specific expression. By regulating actin filament dynamics, Tmods participate in neurite outgrowth, dendritic spine formation, and synaptic morphology, thereby contributing to structural and functional neural plasticity. Dysregulation of Tmods has been demonstrated in several neurodegenerative and neuropsychiatric diseases, such as Alzheimer's disease, epilepsy, Down syndrome, and addictive behaviors. Currently, compared to cancer and cardiovascular diseases, the roles and mechanisms of altered Tmod expression in neurological diseases remain poorly understood. In this article, we provided an overview on the physiological roles and crucial functions of Tmods in the brain, summarized the recent advances in alterations of Tmods in neurodegenerative and neuropsychiatric diseases, and discussed their implications and potential contributions to disease pathology and treatment. This review may expedite future studies to delineate the roles and molecular mechanisms of Tmods in brain physiology and pathology, ultimately promoting the development of novel diagnostic and therapeutic strategies for related neurological diseases.
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spelling doaj-art-b13d7c9445df4b08a6702a2d7f32d1762025-08-20T02:48:18ZengElsevierNeurobiology of Disease1095-953X2025-09-0121310700610.1016/j.nbd.2025.107006Role of Tropomodulins in brain physiology and pathologyChuan Hong0Xiaopeng Liu1Zhou Zhou2Yuan Xing3Zixuan Cao4Yan-Zhong Chang5Guofen Gao6Ministry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Collaborative Innovation Center for Eco-Environment; Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China; Hebei Institute of Metrology, Shijiazhuang 050000, ChinaKey Laboratory of Clinical Neurology, Ministry of Education, Hebei Medical University; Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaMinistry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Collaborative Innovation Center for Eco-Environment; Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, ChinaMinistry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Collaborative Innovation Center for Eco-Environment; Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, ChinaMinistry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Collaborative Innovation Center for Eco-Environment; Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, ChinaMinistry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Collaborative Innovation Center for Eco-Environment; Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China; Corresponding authors at: No. 20, Nan Er Huan East Road, Hebei Normal University, Shijiazhuang 050000, China.Ministry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Collaborative Innovation Center for Eco-Environment; Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China; Corresponding authors at: No. 20, Nan Er Huan East Road, Hebei Normal University, Shijiazhuang 050000, China.Actin dynamics are crucial for the morphogenesis and function of neurons in the brain. Tropomodulins (Tmods) belong to a family of actin-binding proteins that cap the pointed-end of actin filaments. There are four Tmod isoforms, and three of which, Tmod1, Tmod2 and Tmod3, are expressed in the brain, with Tmod2 exhibiting neuronal specific expression. By regulating actin filament dynamics, Tmods participate in neurite outgrowth, dendritic spine formation, and synaptic morphology, thereby contributing to structural and functional neural plasticity. Dysregulation of Tmods has been demonstrated in several neurodegenerative and neuropsychiatric diseases, such as Alzheimer's disease, epilepsy, Down syndrome, and addictive behaviors. Currently, compared to cancer and cardiovascular diseases, the roles and mechanisms of altered Tmod expression in neurological diseases remain poorly understood. In this article, we provided an overview on the physiological roles and crucial functions of Tmods in the brain, summarized the recent advances in alterations of Tmods in neurodegenerative and neuropsychiatric diseases, and discussed their implications and potential contributions to disease pathology and treatment. This review may expedite future studies to delineate the roles and molecular mechanisms of Tmods in brain physiology and pathology, ultimately promoting the development of novel diagnostic and therapeutic strategies for related neurological diseases.http://www.sciencedirect.com/science/article/pii/S0969996125002220TropomodulinsActin filamentsDendriteSynaptic plasticityNeurological disorders
spellingShingle Chuan Hong
Xiaopeng Liu
Zhou Zhou
Yuan Xing
Zixuan Cao
Yan-Zhong Chang
Guofen Gao
Role of Tropomodulins in brain physiology and pathology
Neurobiology of Disease
Tropomodulins
Actin filaments
Dendrite
Synaptic plasticity
Neurological disorders
title Role of Tropomodulins in brain physiology and pathology
title_full Role of Tropomodulins in brain physiology and pathology
title_fullStr Role of Tropomodulins in brain physiology and pathology
title_full_unstemmed Role of Tropomodulins in brain physiology and pathology
title_short Role of Tropomodulins in brain physiology and pathology
title_sort role of tropomodulins in brain physiology and pathology
topic Tropomodulins
Actin filaments
Dendrite
Synaptic plasticity
Neurological disorders
url http://www.sciencedirect.com/science/article/pii/S0969996125002220
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AT yuanxing roleoftropomodulinsinbrainphysiologyandpathology
AT zixuancao roleoftropomodulinsinbrainphysiologyandpathology
AT yanzhongchang roleoftropomodulinsinbrainphysiologyandpathology
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