Disruption of axonal transport in neurodegeneration
Sarah H. Berth, Thomas E. Lloyd
Sarah H. Berth, Thomas E. Lloyd
Published June 1, 2023
Citation Information: J Clin Invest. 2023;133(11):e168554. https://doi.org/10.1172/JCI168554.
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Disruption of axonal transport in neurodegeneration

Abstract

Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of newly synthesized macromolecules and organelles from the cell body to the synapse and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysregulation of axonal transport occurs early in neurodegenerative diseases and plays a key role in axonal degeneration. Here, we provide an overview of mechanisms for regulation of axonal transport; discuss how these mechanisms are disrupted in neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, hereditary spastic paraplegia, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease; and discuss therapeutic approaches targeting axonal transport.

Authors

Sarah H. Berth, Thomas E. Lloyd

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Figure 1

Axonal transport in neurons.

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Axonal transport in neurons. Neurons are compartmentalized, with long ax...
Neurons are compartmentalized, with long axons. Delivery of organelles in the axon is performed via the motor proteins kinesin and dynein, which carry cargoes along microtubule tracks. Kinesin is responsible for anterograde transport of organelles, from the soma to the presynaptic terminal. Dynein is responsible for retrograde transport of organelles from the presynaptic terminal to the cell body. Dynein processivity is enhanced via binding to the essential cofactor dynactin and a cargo adaptor.