Axonal transport deficits and neurodegenerative diseases

Axonal transport delivers proteins, lipids, mRNA and mitochondria to the distal synapse and clears recycled or misfolded proteins. Such transport is involved in neurotransmission, neural trophic signalling and stress insult responses.Cargoes are conveyed along the microtubule tracks in axons by motor proteins.Disturbances in axonal transport are key pathological events that contribute to neurodegeneration in Alzheimer's disease, polyglutamine diseases, hereditary spastic paraplegia, Charcot–Marie–Tooth disease, amyotrophic lateral sclerosis and Parkinson's disease.The identification of mutations in genes encoding motor proteins in patients with neurodegenerative diseases strongly supports the view that defective intracellular transport can directly trigger neuron degeneration.Axonal transport deficits might arise through various mechanisms, including defects in cytoskeletal organization, impairment of motor protein attachment to microtubules, altered kinase activities, destabilization of motor–cargo binding and/or mitochondrial energetic breakdown.Autophagy and RNA metabolism might also interfere with the efficiency of axonal transport.