Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease is marked by a progressive death of motor neurons, and is invariably fatal. A small percent of ALS patients have an inherited mutation in the gene encoding the protein superoxide dismutase 1 (SOD1); this mutation is thought to cause a conformational change in the protein and cause it to not function properly. However, over 90% of all ALS cases are sporadic, with no clearly associated risk factors or inherited causes. A study published online in Nature Neuroscience now reports that SOD1 in sporadic ALS patients also shows similar shape changes and may cause motor neuron death in the same way as the mutated SOD1 found in some inherited ALS cases
Daryl Bosco, Robert Brown and colleagues studied mutant SOD1, SOD1 from ALS patients with no genetic mutation, and normal SOD1 that had been damaged by oxidization — which typically occurs during cellular stress, and may be a possible cause of ALS. They found that all three forms of the protein had the same specific shape change. The mis-folding of SOD1 prevented transport of molecules down the axon of the motor neuron, which then killed the neurons.
These findings suggest that a particular shape change of SOD1 is the common source of cell death in most forms of ALS. Therefore research on the inherited form of the disease — which is much easier to model in mice — may help discover treatments that will be useful in future for all ALS patients.