Yeast Cells May Provide Insight Into Degenerative Neurologic Diseases
NEW YORK (Reuters Health) - In two new studies reported in the December 5th issue of Science, researchers used yeast cells to investigate how alpha-synuclein and other proteins may contribute to the pathogenesis of degenerative neurologic disorders, such as Huntington's disease.
In one study, Dr. Susan Lindquist and Dr. Tiago Fleming Outeiro looked at the expression of alpha-synuclein in Saccharomyces cerevisiae.
The researchers found that before forming cytoplasmic inclusions, the protein seemed to associate with the plasma membrane in a highly selective fashion. Once expressed, alpha-synuclein had a number of effects, including inhibition of phospholipase D, induction of lipid droplet accumulation, and alteration of vesicle trafficking.
Yeast cells provide "an opportunity to dissect the molecular pathways underlying normal alpha-synuclein biology and the pathogenic consequences of its misfolding," the researchers note.
In the second study, Dr. Paul J. Muchowski, from the University of Washington in Seattle, and colleagues investigated yeast genes that increase the toxicity of alpha-synuclein or a mutant huntingtin fragment.
The researchers identified 138 genes that enhanced the toxicity of the proteins. Except for one gene, the genes affected the toxicity of either protein but not both.
Genes that made the huntingtin fragment more toxic seemed to be involved in cell processes related to the stress response, protein folding, and ubiquitin-dependent protein catabolism. By contrast, those that increased alpha-synuclein toxicity were involved in processes, such as lipid metabolism and vesicle-mediated transport.
"The results from yeast screens clearly indicate that toxicity mediated by alpha-synuclein and a mutant huntingtin fragment is regulated by nonoverlapping sets of conserved genes and pathways," the authors state. "Collectively, these results suggest that distinct pathogenic mechanisms may underlie Huntington's disease and Parkinson's disease."
Source: Science 2003;302:1769-1775. [ Google search on this article ]