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Genetics. 2015 Oct;201(2):377-402. doi: 10.1534/genetics.115.179457.

Drosophila as an In Vivo Model for Human Neurodegenerative Disease.

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Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104


With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research.


ALS; Drosophila; FTD; FlyBook; genetic pathways; polyglutamine disease; protein toxicity

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