Journal article
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Proteomics-based monitoring of pathway activity reveals that blocking diacylglycerol biosynthesis rescues from alpha-synuclein toxicity
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Soste, Martin
Institute of Biochemistry, Department of Biology, ETH Zurich, Switzerland - Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Switzerland -
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Charmpi, Konstantina
CECAD, University of Cologne, Germany - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany
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Lampert, Fabienne
Institute of Biochemistry, Department of Biology, ETH Zurich, Switzerland
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Gerez, Juan Atilio
Laboratory of Physical Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Switzerland
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Oostrum, Marcvan
Institute of Biochemistry, Department of Biology, ETH Zurich, Switzerland -
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Malinovska, Liliana
Institute of Biochemistry, Department of Biology, ETH Zurich, Switzerland - Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Switzerland
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Boersema, Paul Jonathan
Institute of Biochemistry, Department of Biology, ETH Zurich, Switzerland - Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Switzerland
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Prymaczok, Natalia Cecilia
Laboratory of Physical Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Switzerland
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Riek, Roland
Laboratory of Physical Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Switzerland
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Peter, Matthias
Institute of Biochemistry, Department of Biology, ETH Zurich, Switzerland
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Vanni, Stefano
Department of Biology, University of Fribourg, Switzerland
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Beyer, Andreas
CECAD, University of Cologne, Germany - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany
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Picotti, Paola
Institute of Biochemistry, Department of Biology, ETH Zurich, Switzerland - Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Switzerland -
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Published in:
- Cell Systems. - 2019, vol. 9, no. 3, p. 309-320.e8
English
Proteinaceous inclusions containing alpha-synuclein (α-Syn) have been implicated in neuronal toxicity in Parkinson’s disease, but the pathways that modulate toxicity remain enigmatic. Here, we used a targeted proteomic assay to simultaneously measure 269 pathway activation markers and proteins deregulated by α-Syn expression across a panel of 33 Saccharomyces cerevisiae strains that genetically modulate α-Syn toxicity. Applying multidimensional linear regression analysis to these data predicted Pah1, a phosphatase that catalyzes conversion of phosphatidic acid to diacylglycerol at the endoplasmic reticulum membrane, as an effector of rescue. Follow-up studies demonstrated that inhibition of Pah1 activity ameliorates the toxic effects of α-Syn, indicate that the diacylglycerol branch of lipid metabolism could enhance α-Syn neuronal cytotoxicity, and suggest a link between α-Syn toxicity and the biology of lipid droplets.
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Faculty
- Faculté des sciences et de médecine
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Department
- Département de Biologie
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Language
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Classification
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Biological sciences
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License
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License undefined
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Identifiers
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Persistent URL
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https://folia.unifr.ch/unifr/documents/308112
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