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

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 signalling 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.