Axonal transport and neurological disease

• Published in: Nature reviews. Neurology Vol. 15; no. 12; pp. 691 - 703
• Main Authors: Sleigh, James N., Rossor, Alexander M., Fellows, Alexander D., Tosolini, Andrew P., Schiavo, Giampietro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-12-2019; Nature Publishing Group
• Subjects: 692/617/375/365; 692/617/375/366; Animals; Axonal Transport - physiology; Axons; Axons - metabolism; Axons - pathology; Care and treatment; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Development and progression; Disease; Health aspects; Humans; Medicine; Medicine & Public Health; Microtubules - genetics; Microtubules - metabolism; Molecular motors (Biochemistry); Mutation; Nervous system; Nervous system diseases; Nervous System Diseases - diagnosis; Nervous System Diseases - genetics; Nervous System Diseases - metabolism; Neurology; Pathogenesis; Physiological aspects; Protein Transport - physiology; Review Article; Risk factors; United Kingdom
• ISSN: 1759-4758; 1759-4766
• DOI: 10.1038/s41582-019-0257-2

Axonal transport is the process whereby motor proteins actively navigate microtubules to deliver diverse cargoes, such as organelles, from one end of the axon to the other, and is widely regarded as essential for nerve development, function and survival. Mutations in genes encoding key components of the transport machinery, including motor proteins, motor adaptors and microtubules, have been discovered to cause neurological disease. Moreover, disruptions in axonal cargo trafficking have been extensively reported across a wide range of nervous system disorders. However, whether these impairments have a major causative role in, are contributing to or are simply a consequence of neuronal degeneration remains unclear. Therefore, the fundamental relevance of defective trafficking along axons to nerve dysfunction and pathology is often debated. In this article, we review the latest evidence emerging from human and in vivo studies on whether perturbations in axonal transport are indeed integral to the pathogenesis of neurological disease.
Axonal transport is the process whereby motor proteins navigate microtubules to deliver diverse cargoes from one end of the axon to the other. In this Review, Schiavo and colleagues explore the link between perturbations in axonal transport and neurological disease.
Key points
Mutations in various genes encoding components of the axonal transport machinery have been implicated in the pathogenesis of neurological diseases.
Defective axonal trafficking has been linked to many nervous system disorders, but whether it is a cause or consequence of neuropathology remains largely unresolved.
Intravital imaging of transport in axons of live mice provides some of the most compelling evidence that trafficking disturbances contribute to neuronal dysfunction.
Targeting of specific mechanisms of axonal transport might be a valid therapeutic strategy to treat neurological disease.