Title: Characterization of alpha-synuclein aggregation and synergistic toxicity with protein tau in yeast
Authors: Zabrocki, Piotr
Pellens, Klaartje
Vanhelmont, Thomas
Vandebroek, Tom
Griffioen, Gerard
Wera, Stefaan
Van Leuven, Freddy
Winderickx, Joris # ×
Issue Date: Mar-2005
Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies
Series Title: FEBS Journal vol:272 issue:6 pages:1386-1400
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.
ISSN: 1742-464X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Molecular Physiology of Plants and Micro-organisms Section - miscellaneous
Associated Laboratories - miscellaneous (-)
Laboratory for Functional Biology (-)
Laboratory of Molecular Biology of Leukemia
× corresponding author
# (joint) last author

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