alpha-Synuclein, oxidative stress and apoptosis from the perspective of a yeast model of Parkinson's disease.
The neuronal protein alpha-synuclein (alpha-syn) has been suggested to be one of the factors linked to Parkinson's disease (PD). Several organisms, including the rat, mouse, worm, and fruit fly, are being used to study alpha-syn pathobiology. A new model organism was recently added to this armamentarium: the budding yeast Saccharomyces cerevisiae. The yeast system recapitulates many of the findings made with higher eukaryotes. For example, yeast cells expressing alpha-syn accumulate lipid droplets, have vacuolar/lysosomal defects, and exhibit markers of apoptosis, including the externalization of phosphatidylserine, the release of cytochrome c, and the accumulation of reactive oxygen species. This MiniReview focuses on the mechanisms by which alpha-syn induces oxidative stress and the mechanisms by which yeast cells respond to this stress. Three classes of therapeutics are discussed.
Witt
Stephan N
SN
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA. switt1@lsuhsc.edu
Flower
Todd R
TR
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000378:metabolism* / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000975:Antioxidants; D061945:Caspase Inhibitors; D050884:HSP72 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D020169:Caspases; D042967:Electron Transport Complex I; D004298:Dopamine