Characterization of Aggregation-induced Toxicity by ?-synuclein in Yeast / 微生物学通报

ABSTRACT

Parkinson's disease(PD) is the most common neurodegenerative movement disorder and ?-synuclein plays an important role in its development.Using the genetically tractable Saccharomyces cere-visiae as a model system,the phenotypic repercussions and potential mechanisms of ?-synuclein-induced cytotoxicity are characterized through modulating its expression level and other cellular factors.Aggrega-tion-induced toxicity is more dramatic upon elevated expression of ?-synuclein than that induced at moder-ate levels of expression.The induced toxicity is also enhanced by reagents such as dimethyl sulfoxide,which increase intracellular levels of phospholipid and membrane,as well as ferrous ions and hydrogen peroxide,both of which cause oxidative stresses in yeast cells.In contrast,over-expression of yeast homologue of hu-man chaperone DJ-1,YDR533C,markedly alleviate the inhibition of growth afflicted by exogenous expres-sion of ?-synuclein.Taken together,the data presented suggest a role for protein folding machinery together with quality control system in dealing with the aggregation of ?-synuclein.