From fruit fly to bedside: translating lessons from Drosophila models of neurodegenerative disease.

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Fly models have been developed for a variety of neurodegenerative disorders, and the field is beginning to harness the power of Drosophila genetics to dissect pathways of disease pathogenesis and identify targets for therapeutic intervention. In this review, we emphasize the most recent accomplishments and chart the potential rewards in translating lessons from Drosophila models to clinical therapeutics. The conservation of human disease genes in the Drosophila genome forms the basis for several recent investigations of the normal biological functions of genes implicated in neurodegenerative disease. In addition, transgenic approaches continue to expand the list of diseases modeled in Drosophila that now includes Parkinson's disease, Alzheimer's disease, Huntington's disease, and several spinocerebellar ataxias. Studies based on these models suggest that protein folding and degradation pathways play an important role in Parkinson's disease and the polyglutamine repeat disorders, and that kinases and apoptotic pathways may modulate neurodegeneration in tauopathies. Ongoing genetic studies with Drosophila neurodegenerative disease models promise to enhance our understanding of disease pathogenesis and generate target lists for future investigational research and drug development. The next challenge will be distilling a growing number of possible targets into a shortlist for fast-track drug design and clinical trials. With the advent of neurodegenerative disease models, the fruit fly is rapidly assuming a unique niche in bench to bedside research.