Axonal transport, defects

Collard, J.-F., Cote, F. and Julien, J.-P. Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375 61-64,1995. 

Peripheral neuropathy is seen in patients with this syndrome, which may be related to abnormal axonal transport, as a consequence of a defect in microtubules (79). Patients are susceptible to recurrent infections, especially with Staphylococcus aureus and beta-hemolytic streptococci. 

Millecamps S, Robertson J, Laiiviere R, MaUet J, Juhen JP (2006) Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin. J Neurochem 98 926-938... 

Several authors have provided evidence that pathological-length Qn repeats promote aberrant protein interactions that cause defects in axonal transport (Gunawardena and Goldstein, 2005 Smith et al 2009 Schweitzer et al., 2009 Wu et al.,... 

In a Drosophila model of tauopathy in which abnormal human tau mediates neuronal dysfunction characterized by microtubule destabilization, axonal transport disruption, synaptic defects and behavioral impairments, the microtubule-stabilizing drug, NAPVSIPQ (NAP) (davunetide), prevents as well as reverses these phenotypes even after they have become established [341],... 

The molecular mechanism associated with the pathogenesis of ALS still remains elusive, but oxidative stress, mitochondrial impairment, protein mis-folding, cytoskeletal abnormalities and defective axonal transport, excitotoxicity. 

Neurons cannot synthesise proteins along the axon and are particularly dependent on vesicular transport to provide them. Many neurodegenerative disorders show examples of defects in the cytoskeletal tracts, which sustain neuronal shape and trafflcking, or defects in the motors, which provide energy for vesicle/organelle movement, including mitochondria. 

Sodium-lithium countertransport, anion exchange, and the leak mechanism are the most important transport routes for lithium in vivo. Lithium appears to substitute for sodium in all of these pathways in the erythrocytes (131) and also in the squid axon membrane (132). Sodium-lithium countertransport has been claimed to be abnormal in patients suffering from essential hypertension and in their close relatives (133). However, despite a decade of experimental study by many different laboratories, there is no consensus with regard to the true basis of the membrane defect, if indeed it is really present. Nor is it clear under what precise conditions the abnormality is manifest (134). 

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