Larger Clusters of ALS Protein Can Protect Brain Cells

• Small aggregates (trimers) rather than larger aggregates of abnormal SOD1 protein found to be highly toxic to nerve cells resulting in their damage and death in amyotrophic lateral sclerosis (ALS).
• ALS or Lou Gehrig's disease is a rare but progressive neurological condition marked by damage to nerve cells in brain and spinal cord causing difficulty of voluntary muscle activity such as walking, talking and chewing.

Aim of Study

• Many neurodegenerative diseases such as Alzheimer's disease ALS, Parkinson's disease and Huntington's disease are characterized by formation of large protein aggregates within nerve cells.
• Several drug treatments have been developed to target and eliminate these larger abnormal protein clusters but they have been found to be ineffective in several clinical trials.
• Additionally, there is no evidence to show that these large protein aggregates are harmful to nerve cells; on the other hand, earlier studies have shown that "trimer" structures made of just three copies of the SOD1 protein are toxic and cause injury and death to neurons in ALS.

Details of Study

• The team found a mutation that stabilizes the protein aggregates in the trimeric form, which normally occurs only transiently, thereby enabling its analysis.

• The team also successfully expressed mutant forms of the SOD1 protein (not necessarily trimers) in test cells that closely resembled neurons affected in ALS.

Key Observations of Study

• When the test cells expressed SOD1 mutants predominantly forming trimers, the neurons died much more quickly than control cells expressing normal SOD1 protein.

• The trimer-expressing cells even died more quickly than cells expressing other mutant forms of SOD1 protein similar to those found in severe hereditary ALS cases.