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- W2910643694 abstract "The extension of the amyloid hypothesis to include non-protein metabolite assemblies invokes a paradigm for the pathology of inborn error of metabolism disorders. However, a direct demonstration of the assembly of metabolite amyloid-like structures has so far been provided only in vitro. Here, we established an in vivo model of adenine self-assembly in yeast, in which toxicity is associated with intracellular accumulation of the metabolite. Using a strain blocked in the enzymatic pathway downstream to adenine, we observed a non-linear dose-dependent growth inhibition. Both the staining with an indicative amyloid dye and anti-adenine assemblies antibodies demonstrated the accumulation of adenine amyloid-like structures, which were eliminated by lowering the supplied adenine levels. Treatment with a polyphenol inhibitor reduced the occurrence of amyloid-like structures while not affecting the dramatic increase in intracellular adenine concentration, resulting in inhibition of cytotoxicity, further supporting the notion that toxicity is triggered by adenine assemblies." @default.
- W2910643694 created "2019-01-25" @default.
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- W2910643694 date "2019-01-08" @default.
- W2910643694 modified "2023-10-02" @default.
- W2910643694 title "Fibril formation and therapeutic targeting of amyloid-like structures in a yeast model of adenine accumulation" @default.
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- W2910643694 doi "https://doi.org/10.1038/s41467-018-07966-5" @default.
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- W2910643694 hasPublicationYear "2019" @default.
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