The microtubule-associated protein Tau is an enigmatic protein. Its phosphorylation plays a pivotal role in normal physiology while its hyperphosphorylation occurs in neurodegenerative disorders like Alzheimer’s disease, Pick’s disease and FTDP-17. As with other neurological diseases, Drosophila melenogaster allows the power of genetic analysis to help decipher the role of Tau in the disease process and to probe molecular and genetic interactions that are important in preventing or enhancing its deleterious effects. We express transgenes encoding human Tau in the entire fly central nervous system and in combination with a powerful proteomic approach we probe molecular interactions that are important in preventing or enhancing its deleterious effects. We further validate the results of the proteomic screens above by genetic and molecular analyses for the enhancement/suppression of Tau-dependent neurodegenerative phenotypes. As we gain a deeper understanding of the cellular regulation mechanisms of Tau function, we will shed more light on the complex role of Tau in the aetiopathogenesis of neurodegeneration.

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