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Defects in Axonal Transport in Inherited Neuropathies
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Axonal transport is a highly complex process essential for sustaining proper neuronal functioning. Disturbances can result in an altered neuronal homeostasis, aggregation of cargoes, and ultimately a dying-back degeneration of neurons. The impact of dysfunction in axonal transport is shown by genetic defects in key proteins causing a broad spectrum of neurodegenerative diseases, including inherited peripheral neuropathies. In this review, we provide an overview of the cytoskeletal components, molecular motors and adaptor proteins involved in axonal transport mechanisms and their implication in neuronal functioning.
In addition, we discuss the involvement of axonal transport dysfunction in neurodegenerative diseases with a particular focus on inherited peripheral neuropathies. Lastly, we address some recent scientific advances most notably in therapeutic strategies employed in the area of axonal transport, patient-derived iPSC models, in vivo animal models, antisense-oligonucleotide treatments, and novel chemical compounds.
Axonal transport is a highly complex process allowing movement of molecules and organelles within neurons over tremendous distances towards presynaptic nerve termini anterograde transport , and transferring material from the periphery back to the neuronal soma retrograde transport. This intracellular trafficking is crucial for sustaining proper neuronal functioning as well as clearing misfolded proteins or damaged organelles to avoid accumulation of harmful aggregates.
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