Modeling age-related diseases in Drosophila: can this fly?

Human neurodegenerative diseases are characterized by progressive neuronal cell loss often resulting in memory and cognitive decline, motor dysfunction, and ultimately premature death. Despite the prevalence of these diseases, there are no effective cures. Insight into many of these syndromes has come from the identification of single gene mutations that are associated with inherited forms of the disease. This has led to the development of animal models in which the pathogenesis caused by these genes can be rigorously examined. Due to their short life span and powerful genetic potential, several attempts have been made to model neurodegenerative diseases in the fruit fly Drosophila melanogaster. This review will describe how these models were generated and how faithfully they recapitulate human disease. In addition, how fly models can be used to identify genetic modifiers of known disease genes and what these have revealed about the biochemical pathways underlying disease pathogenesis is discussed. Finally, the review will describe how fly models can be used to identify new therapeutic targets and test the effectiveness of new drugs.