The microtubule-binding protein tau has been implicated in the pathogenesis of Alzheimer's disease and related disorders. However, the mechanisms underlying tau-mediated neurotoxicity remain unclear. We created a genetic model of tau-related neurodegenerative disease by expressing wild-type and mutant forms of human tau in the fruit fly Drosophila melanogaster. Transgenic flies showed key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary tangle formation that is seen in human disease and some rodent tauopathy models. This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity.

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Background: ⌬Np63 expression correlates with an epithelial phenotype and adverse clinical outcome. Results: ⌬Np63␣ suppressed ZEB1/2 and invasion in part by promoting miR-205 transcription, and tumor miR-205 expression is a marker of poor survival. Conclusion: ⌬Np63␣ inhibits EMT in part via miR-205. Significance: We show that ⌬Np63␣ directly regulates miR-205 and that these effects contribute to EMT suppression. The results provide important insight into the biology of lethal bladder cancer.

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