title: Characterization of alpha-synuclein aggregation and synergistic toxicity with protein tau in yeast.
abstract: A yeast model was generated to study the mechanisms and phenotypical repercussions of expression of alpha-synuclein as well as the coexpression of protein tau. The data show that aggregation of alpha-synuclein is a nucleation-elongation process initiated at the plasma membrane. Aggregation is consistently enhanced by dimethyl sulfoxide, which is known to increase the level of phospholipids and membranes in yeast cells. Aggregation of alpha-synuclein was also triggered by treatment of the yeast cells with ferrous ions, which are known to increase oxidative stress. In addition, data are presented in support of the hypothesis that degradation of alpha-synuclein occurs via autophagy and proteasomes and that aggregation of alpha-synuclein disturbs endocytosis. Reminiscent of observations in double-transgenic mice, coexpression of alpha-synuclein and protein tau in yeast cells is synergistically toxic, as exemplified by inhibition of proliferation. Taken together, the data show that these yeast models recapitulate major aspects of alpha-synuclein aggregation and cytotoxicity, and offer great potential for defining the underlying mechanisms of toxicity and synergistic actions of alpha-synuclein and protein tau.
authors.affiliation: Functional Biology, Katholieke Universiteit Leuven, Belgium.
authors.forename: Piotr
authors.initials: P
authors.lastname: Zabrocki
authors.forename: Klaartje
authors.initials: K
authors.lastname: Pellens
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanhelmont
authors.forename: Tom
authors.initials: T
authors.lastname: Vandebroek
authors.forename: Gerard
authors.initials: G
authors.lastname: Griffioen
authors.forename: Stefaan
authors.initials: S
authors.lastname: Wera
authors.forename: Fred
authors.initials: F
authors.lastname: Van Leuven
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx
mesh_terms: D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins; D046988:Proteasome Endopeptidase Complex; D004121:Dimethyl Sulfoxide