A Curious Clue to Parkinson’s
Drugs that boost protein aggregation could provide a new route to treatment
Source: “Pharmacological Promotion of Inclusion Formation: A Therapeutic Approach for Huntington’s and Parkinson’s Diseases”
Ruth Bodner et al.
Proceedings of the National Academy of Sciences 103(11): 4246-4251
Results: Ruth Bodner, a postdoc at MIT’s Center for Cancer Research, biology professor David Housman, and colleagues have identified a compound that can increase protein aggregation in cellular models of Parkinson’s and Huntington’s disease. When treated with the compound, called B2, Parkinson’s cells that normally would have died survived. And Huntington’s cells treated with the compound had better–functioning proteosomes – the cellular “garbage cans” that are often dysfunctional in the disease.
Why it matters: Abnormal aggregations of protein are a characteristic of many types of neurodegenerative disease, including Huntington’s, Parkinson’s, and Alzheimer’s. However, there is continuing scientific disagreement over the nature of these aggregations. While they correlate with some aspects of the diseases, recent evidence suggests that they may be harmless or even helpful in preventing neuro-toxicity. The MIT study builds on this last possibility by demonstrating that increased protein aggregation can improve the health of cells modeling neurodegenerative disease.
Methods: Scientists conducted a large-scale drug screen, examining how different compounds affected cells that had been engineered to produce mutant proteins implicated in Parkinson’s disease and Huntington’s disease.
Next Step: The MIT researchers conducting the experiments would like to figure out how the B2 compound works. Cells usually get rid of misshapen proteins by breaking them down in proteosomes, but this mechanism may get overloaded in neurodegenerative disease. Housman and Bodner theorize that the compound works by helping the cell sequester into clumps the single proteins or smaller aggregates of proteins that might be harmful to it.