A novel method to discover genes that protect cells from alpha synuclein

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DESCRIPTION (provided by applicant): We have been using the budding yeast Saccharomyces cerevisiae to study the Parkinson's disease- related protein alpha synuclein (a-syn). We have discovered that yeast cells expressing wild-type a-syn (WT), or either of the two inherited mutants, A53T or A30P, exhibit several markers of apoptosis: externalization of phosphatidylserine, the accumulation of reactive oxygen species, and the release of cytochrome c from mitochondria into the cytosol. We also discovered that yeast cells expressing any of the three a-syns are very sensitive to killing by hydrogen peroxide, which is known inducer of apoptosis in yeast. This finding has been exploited to create a unique genetic screen. Genes from a high copy library that rescue hydrogen peroxide sensitivity may also suppress other traits of a-syn expression and provide insights into the mechanisms by which a-syn causes cell death. This method allows us to screen libraries of genes- genes from any organism-to discover genes that protect against a-syn toxicity.