{"title":"Filamin A in focus: unravelling the multifaceted roles of filamin A in neurodevelopment and neurological disorders.","authors":"Longbo Zhang","doi":"10.1093/brain/awaf180","DOIUrl":null,"url":null,"abstract":"Neurodevelopment is an intricate process encompassing the proliferation, differentiation, migration, and maturation of neural cells. Disruptions in these tightly regulated events can lead to a variety of neurodevelopmental disorders. Filamin A (FLNA), a key actin-binding protein, plays a pivotal role in regulating neuronal migration, morphological development, and synaptic connectivity by modulating actin cytoskeletal dynamics and interacting with various signaling pathways. FLNA mutations are implicated in several neurodevelopmental disorders, such as periventricular nodular heterotopia (PVNH), leading to neurological symptoms such as epilepsy, intellectual disability, and cognitive impairments. In this review, we delve into FLNA's multifaceted role in neurodevelopment, with a particular focus on its contributions to neuronal migration, dendritic and axonal growth, and mechanotransduction. Additionally, we examine how FLNA dysregulation leads to neurodevelopmental abnormalities, providing insights into its potential as a therapeutic target. By elucidating the molecular mechanisms through which FLNA governs neurodevelopment, we aim to advance our understanding of its crucial role in both brain formation and disease pathogenesis.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"27 1","pages":""},"PeriodicalIF":10.6000,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/brain/awaf180","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Neurodevelopment is an intricate process encompassing the proliferation, differentiation, migration, and maturation of neural cells. Disruptions in these tightly regulated events can lead to a variety of neurodevelopmental disorders. Filamin A (FLNA), a key actin-binding protein, plays a pivotal role in regulating neuronal migration, morphological development, and synaptic connectivity by modulating actin cytoskeletal dynamics and interacting with various signaling pathways. FLNA mutations are implicated in several neurodevelopmental disorders, such as periventricular nodular heterotopia (PVNH), leading to neurological symptoms such as epilepsy, intellectual disability, and cognitive impairments. In this review, we delve into FLNA's multifaceted role in neurodevelopment, with a particular focus on its contributions to neuronal migration, dendritic and axonal growth, and mechanotransduction. Additionally, we examine how FLNA dysregulation leads to neurodevelopmental abnormalities, providing insights into its potential as a therapeutic target. By elucidating the molecular mechanisms through which FLNA governs neurodevelopment, we aim to advance our understanding of its crucial role in both brain formation and disease pathogenesis.
期刊介绍:
Brain, a journal focused on clinical neurology and translational neuroscience, has been publishing landmark papers since 1878. The journal aims to expand its scope by including studies that shed light on disease mechanisms and conducting innovative clinical trials for brain disorders. With a wide range of topics covered, the Editorial Board represents the international readership and diverse coverage of the journal. Accepted articles are promptly posted online, typically within a few weeks of acceptance. As of 2022, Brain holds an impressive impact factor of 14.5, according to the Journal Citation Reports.