Role of the proteasome in fly models of neurodegeneration

Most neurodegenerative disorders are associated with aggregates of ubiquitinated proteins, such as Lewy bodies in Parkinson's disease and neurofibrillary tangles in Alzheimer's disease. Although the etiology of the sporadic forms of these disorders remains elusive, these observations support our idea that proteasome impairment is an important risk factor in neurodegeneration. Proteasome dysfunction is, thus, expected to be a pivotal link between environmental and genetic factors that are implicated in triggering neurodegeneration. Here, we discuss the rationale for the use of Drosophila as a model system for the study of neurodegeneration. As an example of a specific application of this model system, we provide experimental methodology for the assessment of proteasome function by a nondenaturing gel assay, by Western blotting, as well as measurement of ATP levels which are critical for proteasome function. In addition, we discuss immunocytochemical approaches for the study of both the larval and adult Drosophila nervous system.