Yeast Model Shows Alpha-Synuclein's Link to Parkinson's

Researchers into the molecular basis for Parkinson's disease have used a yeast model to study the relationship between the protein produced by the alpha-synuclein gene and the development of Parkinson's disease.

Investigators at the Whitehead Institute for Biomedical Research (Cambridge, MA, USA) created a yeast model for Parkinson's disease by inserting two mutant forms of the alpha-synuclein gene found in patients with Parkinson's disease. A control yeast was created by insertion of a single copy of the normal, wild type alpha-synuclein gene.

Results published in the December 5, 2003, issue of Science revealed that alpha-synuclein associated with the plasma membrane in a highly selective manner, before forming cytoplasmic inclusions through a concentration-dependent, nucleated process. Alpha-synuclein inhibited phospholipase D, induced lipid droplet accumulation, and affected vesicle trafficking. The overexpression of alpha synuclein caused the build up of inclusion bodies in the yeast that eventually had a toxic effect on the cells. The authors speculate that a similar phenomenon occurs in the brain cells of patients with Parkinson's disease, resulting in cell death and neurodegeneration.




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Whitehead Institute for Biomedical Research