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聚焦细丝蛋白A:揭示细丝蛋白A在神经发育和神经疾病中的多方面作用

Filamin A in focus: unravelling the multifaceted roles of filamin A in neurodevelopment and neurological disorders.

作者信息

Zhang Longbo

机构信息

Department of Neurosurgery, Xiangya Hospital, Central South University, Jiangxi (National Regional Center for Neurological Diseases), Nanchang, 330000, China.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China.

出版信息

Brain. 2025 May 14. doi: 10.1093/brain/awaf180.

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.

摘要

神经发育是一个复杂的过程,包括神经细胞的增殖、分化、迁移和成熟。这些受到严格调控的过程出现紊乱会导致多种神经发育障碍。细丝蛋白A(FLNA)是一种关键的肌动蛋白结合蛋白,通过调节肌动蛋白细胞骨架动力学并与各种信号通路相互作用,在调节神经元迁移、形态发育和突触连接方面发挥着关键作用。FLNA突变与几种神经发育障碍有关,如室管膜下结节性异位(PVNH),可导致癫痫、智力残疾和认知障碍等神经症状。在这篇综述中,我们深入探讨FLNA在神经发育中的多方面作用,特别关注其对神经元迁移、树突和轴突生长以及机械转导的贡献。此外,我们研究了FLNA失调如何导致神经发育异常,从而深入了解其作为治疗靶点的潜力。通过阐明FLNA调控神经发育的分子机制,我们旨在加深对其在脑形成和疾病发病机制中关键作用的理解。

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