When the Cytoskeleton Fails: Primary Structural Defects Underlying Disorders with Neurological Involvement

Abstract

Cytoskeletal disorders affecting the nervous system are a diverse group of diseases that display a wide variety of clinical manifestations. Mutations in genes encoding cytoskeletal components disrupt the structural and functional integrity of this complex network, impairing normal development and function of the central and peripheral nervous systems. There are also certain diseases which lead to progressive neurodegeneration, and others which result from an interplay of multiple molecular pathways. This review outlines the primary cytoskeletal disorders affecting the nervous system. To provide a comprehensive overview, these diseases are categorized by their predominantly affected cytoskeletal component—namely microtubules, actin filaments, intermediate filaments, and cytoskeleton-associated proteins. Each category highlights the broader pathophysiological context of the underlying defect rather than an isolated structural disturbance. A deeper understanding of the complex pathophysiology of these disorders may contribute to the discovery of potential therapeutic targets, since current medical management primarily provides symptomatic relief or slows their progression.