Drosophila melanogaster as a Model Organism to Study Human Neurodegenerative Diseases

A great deal of our current understanding about the biology of neurodegenerative diseases has come from studying the function of genes linked to inherited forms of these disorders. Work performed in animal models, including vertebrates as well as invertebrates, has been instrumental in deciphering the cellular, physiological and behavioural deficits arising from the expression of disease-causing genes. Using the fruit fly, Drosophila melanogaster, as a model we examined the normal and aberrant function of two genes linked to the onset of neurodegeneration in humans, presenilin and superoxide dismutase. Drosophila is an extremely versatile model and in many ways is ideal for studying the genetic basis of human disease. The high degree of genetic conservation coupled with low genetic redundancy make this model particularly well suited for studying the function of disease causing genes. We demonstrate a novel genetic,physical and physiological interaction between presenilin and calmodulin and describe how this interaction impacts a very early cellular defect associated with Alzheimer?s Disease, intracellular calcium dyshomeostasis. We also describe progressive locomotory deficits in flies expressing mutant alleles of the superoxide dismutase gene, which have been linked to the onset of familial amyotrophic lateral sclerosis. Collectively, our work demonstrates that Drosophila can be used to study the cellular, physiological and behavioural basis of human neurodegenerative diseases and may provide a model to identify novel therapeutic avenues for neurodegenerative diseases.Ph