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A yeast model for Aβ aggregation exemplifies the role of membrane trafficking and PICALM in cytotoxicity.
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Edité par CCSD ; Cambridge Company of Biologists -
International audience. Alzheimer's disease is the most common neurodegenerative disease, associated with aggregation of Aβ peptides. The exact mechanism of neuronal cell dysfunction in Alzheimer's disease is poorly understood and numerous models have been used to decipher the mechanisms leading to cellular death. Yeast cells might be a good model to understand the intracellular toxicity triggered by Aβ peptides. Indeed, yeast has been used as a model to examine protein functions or cellular pathways that mediate the secretion, aggregation, and subsequent toxicity of proteins associated with human neurodegenerative disorders. In the present study, we use the yeast Saccharomyces cerevisiae as a model system to study the effects of intracellular Aβ in fusion with the green fluorescent protein. We sent this fusion protein into the secretory pathway, and showed that intracellular traffic pathways are necessary to generate toxic species. Yeast PICALM orthologs are involved in cellular toxicity, indicating conservation of the mechanisms of toxicity from mammals to yeast. Finally, our model demonstrates the capacity for intracellular Aβ to cross intracellular membranes and target mitochondrial organelles.
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