Drosophila models of Parkinson's disease

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder principally affecting the dopaminergic neurons of the substantia nigra. The pathogenic mechanisms are unknown and there are currently no cure or disease-modifying therapies. Recent genetic linkage studies have begun to identify single-gene mutations responsible for rare heritable forms of PD and define genetic risk factors contributing to disease prevalence in sporadic cases. These findings provide an opportunity to gain insight into the molecular mechanisms of this disorder through the creation and analysis of appropriate genetic models. One model system that has proven surprisingly tractable for these studies is the fruit fly, Drosophila melanogaster. Analysis of a number of Drosophila models of PD has revealed some profound and sometimes surprising insights into PD pathogenesis. Moreover, these models can be used to investigate potential therapeutic strategies that may be effective in vivo, and tests have highlighted the efficacy of a number of neuroprotective compounds. Here, I review the methodologies employed in developing the various Drosophila models, and the recent advances that these models in particular have contributed to our understanding of the mechanisms that underlie PD pathogenesis and possible treatment strategies.