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UMMS researchers identify protein associated with sporadic ALS
Date:10/18/2010

ALS, he hoped that one day research would provide insight into the more common sporadic form of the disease. "It's been hypothesized that there are common pathogenic pathways between familial and sporadic ALS," said Brown. "Our new findings strongly suggest that is the case."

To determine whether the SOD1 protein found in sporadic ALS cases had become toxic via non-inherited modifications, Bosco and colleagues showed that an antibody known to bind specifically to mutant SOD1 also binds to SOD1 modified by oxidation indicating that the oxidized SOD1 protein shared characteristics with the mutant SOD1 protein. Additional experiments showed further that in four out of nine samples from individuals with sporadic ALS, the same antibody recognized the SOD1 protein in spinal motor neurons, evidence that the protein had been modified in a similar way as the mutant SOD1 in familial ALS and in samples oxidized in the lab. Moreover, the SOD1 protein extracted from three of these cases proved toxic to the function of motor neurons in an experimental model.

"This research shows that under certain conditions and absent a mutation in the gene, a normal SOD1 protein can have the same toxic characteristics that are found in familial ALS where SOD1 gene is mutated," said Brown. "What's more, we found the presence of these aberrant proteins in select cases of sporadic ALS."

"Until now, factors linking both forms of ALS have been lacking," said Bosco. "These results demonstrate that this protein plays a role in both forms of the disease."

Bosco cautions that while a modified form of the SOD1 protein may play a part in sporadic cases of ALS, it's still unclear what is causing the modification, how many cases may be as a result of the modification or whether it is the primary cause of the disease. "Despite the presence of the normal gene, we show that modifications to the protein made by the gene makes it behave like the toxic, mutated forms of protein," said Bosco.
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Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School
Source:Eurekalert

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