Parkinson's disease: insights from non-traditional model organisms.

Parkinson's disease (PD) was one of the first neurological disorders to have aspects of the disease modeled faithfully in non-human animal species. A key feature of the disease is a diminished control over voluntary movement and progressive depletion of brain dopamine (DA) levels that stems from the large-scale loss of DA-producing neurons. Despite their inherent limitations, rodent and non-human primate models of PD have helped unravel several aspects of PD pathogenesis. Thus, we now have neurotransmitter replacement therapy for PD, and a number of neuroprotective compounds that can be assessed in clinical trials. However, no treatment is currently available that can halt or retard the progressive loss of DA neurons, which underlies PD pathology. Moreover, no therapies can permanently alleviate the clinical features of the disease. The lack of a cure or long-term effective treatment is paralled by our incomplete understanding of the underlying pathomechanisms of the disease. A range of robust, flexible, and complementary animal models will be an invaluable tool with which to unravel the pathogenesis of PD. Here we review the most important contributions made by non-mammalian model organisms. These include zebrafish (Danio rerio), flies (Drosophila melanogaster), anurans (frogs and toads) and nematodes (Caenorhabditis elegans). While it is not anticipated that they will replace rodent and primate-based ones, they offer convenient systems with which to explore the relative contribution made by genetic and environmental factors to PD pathology. In addition, they offer an economic and rapid alternative for testing compounds that target PD. Most importantly, the combined use of these models allow for ongoing research to uncover the basic mechanisms underlying PD pathogenesis. Crown