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Axon Transport Defects

Motor neurons are often extremely long cells with their axons leading from the spinal cord to muscles. The sheer distance that nutrients and other materials must travel back and forth from the cell body to the synapse creates logistical issues. Just the added energy requirement for transport makes these cells vulnerable in a way others aren’t.

A good bit of Packard research has focused on impaired axon transport as a potential cause of ALS, with much work concentrated  on neurofilaments, the long protein tubules in cells that play a key role in stimulating axon growth. One of the hallmarks of ALS is the over-accumulation of neurofilaments in parts of motor neurons. Mice with mutations in neurofilament genes also have poorly functioning motor neurons.

If SOD1 ALS mice are made to overproduce neurofilaments, the mice have longer lifespans. Since the excess neurofilaments collect in the cell body rather than the axons, Packard scientists believe that,  with fewer neurofilaments in the way, axon transport may be improved in these animals.

Axon transport involves more than neurofilaments. Microscopic molecular “motors” can move materials across entire axons. Mutations in the motors’ genes can paralyze mice. One family study showed that a specific mutation in the gene for the motor protein dynactin resulted in members with paralyzed vocal cords.

New Packard work centers on what happens to axon transport of mitochondria – the cell’s powerhouses – in ALS. Early studies show distinct differences in people and animals with ALS.
 

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Our Experts

Johns Hopkins University
Motor neurons can only work properly if the cell’s proteins can get to the right place at the right time. Thomas Lloyd uses the fruit fly Drosophila melanogaster to study how proteins are shuttled between the cell body and the synapse, as interruptions in this process have been linked to ALS. 
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University of Michigan
Sami Barmada wants to answer a very basic question about ALS: why motor neurons? Of all the different types of neurons in the body (and scientists estimate there are probably several hundred), it’s only motor neurons that are affected in ALS. Knowing why this is, Barmada believes, could be the key to developing new potential treatments that could prevent the deterioration and death of motor neurons. 
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