Discovery of new cellular mechanism behind Lou Gehrig's disease

University of Kentucky researchers have discovered a new cellular mechanism that may better explain what causes amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease.

In a paper published in the June 1 issue of the Journal of Biological Chemistry , UK molecular and cellular biochemistry assistant professor Haining Zhu reports on how mutations in the gene that makes superoxide dismutase 1 (SOD1) slows down the intracellular transport of molecules in neurons.

The results of the study by Zhu and his colleagues show that the defective transport of molecules is probably due to the aberrant interaction between the disease-causing SOD1 mutants and a motor complex that is essential to the intracellular transport in neurons. This provides new insight into ways to prevent or slow ALS.

ALS is characterized by the death of neurons that control voluntary muscles, leading to muscle weakness and atrophy. Around 25 percent of the familial forms of the disease have been linked to the mutation in the gene that makes SOD1.
Until now, how the defective variants of the SOD1 protein may interact with other cellular components to cause the disease has remained unclear. Previous studies have shown slowing of transport process in ALS patients and in related animal models. However, it is unknown how the transport process is compromised. The new results from the study by Zhu and his colleagues provide a molecular mechanism for the defective transport in ALS.

The findings are presented in the article "Interaction between Familial Amyotrophic Lateral Sclerosis (ALS)-linked SOD1 Mutants and the Dynein Complex."

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