Causes of ALS: Axon Transport Defects

Motor neurons are often extremely long cells with their axons leading, as they do, from the spinal cord to muscles. That presents problems of carrying needed nutrients and other materials both ways – part of the phenomenon of axon transport. Just the added energy requirement for transport makes these cells vulnerable in a way others aren’t. 

It’s not surprising, then, that researchers have considered flawed axon transport as a possible defect involved in ALS. A good bit of Packard research has centered on neurofilaments – the long protein tubules in cells that play a key role in stimulating axon growth. An odd over-accumulation of neurofilaments in parts of motor neurons is a hallmark of ALS. And mice with mutations in neurofilament genes have been found to have poorly functioning motor neurons.

Packard scientists found it unusual that if the SOD1 mice that model ALS are made to overproduce neurofilaments, they collect in the cell body rather than the axons and that these mice have longer lifespans. The reasoning, they’ve proposed, is that with fewer neurofilaments in the way, axon transport may be improved in these animals.

More than neurofilaments may be involved. Axon transport is made possible by microscopic molecular “motors” that can move materials throughout entire axons. Mutations in the motors’ genes can produce mice with paralysis. And one family study showed a specific mutation that created a flaw in 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 the disease.

Learn more about the research projects funded and coordinated by the Packard Center for ALS Research at Johns Hopkins, and targeted at finding the causes of ALS and a cure. Subscribe to ALS Alert to stay informed about ALS research and clinical trials.