New research identifies key proteins that cause motor neuron death in amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease patients. ALS is a nervous system disease that affects the brain and spinal cord, and gradually weakens muscles that can cause patients to lose their ability to speak, swallow, breathe, and often results in paralysis. There are an estimated 30,000 Americans living with ALS, and it mainly affects patients between the ages of 40 and 70. While there is currently no cure for ALS, new research conducted by the University of North Carolina identified the mutant proteins that cause muscle nerve cells to deteriorate, which could lead to new breakthrough ALS treatments.
Mutant Protein Bonds & ALS
The cause of neurodegenerative diseases like ALS is linked to the aggregation of proteins that effect healthy cells according to researchers. During the study, researchers focused on patients with a subset type of ALS that have variations of a protein called SOD1. The SOD1 protein provides instructions for making an enzyme that is abundant in the body called superoxide dismutase. The purpose of this enzyme is to bind to molecules of copper and zinc that help break down oxygen superoxide molecules that are toxic. However, this process can damage healthy cells if too many superoxide radicals accumulate within a cell.
Researchers revealed through computer structural modeling and live cell experiments that SOD1 collects into mutant clumps of three called trimers. The model reveals that the significance of these SOD1 trimer bonds is that they cause a gradual deterioration within the neuron-like cells that were grown in the lab. The structural modeling of SOD1 also revealed that non-clumped trimers did not affect the lab grown neuron cells. The implications this new research provides a direct link between aggregate mutant proteins like SOD1 and neuron cell death. This accumulation of trimers in neuron cells in essence causes ALS patients to lose the ability to move their arms and legs, and it gradually affects speech, swallowing and breathing that can lead to death.
Next Steps
The next phase of research with this newly found insight is to identify what bonds trimers together, and ways to manipulate this new specie. This new understanding overall reveals how patients develop ALS, and it could be used to prevent or slow down the progression of this disease through new therapeutic ALS drugs. The knowledge of toxic proteins like SOD1 trimers could also provide new insights on the cause of other neurodegenerative diseases like Parkinson’s and Alzheimer’s.
