Neurodegenerative diseases exact an enormous emotional and financial toll on patients, their families, and society. The incidence of these diseases is rapidly rising with the advancing age of our population. Thus, the development of therapies to combat these disorders is of utmost importance to increasing the quality of life for afflicted individuals. The recent identification of alpha-synuclein as a culprit in familial Parkinson's disease and other neurological disorders presents a potential target for therapy. The goal of this research is to identify other genes which interact with alpha-synuclein and contribute to neurodegenerative pathology. We will use a forward genetic approach in an alpha-synuclein transgenic fly model in order to find genes which interact with alpha-synuclein to enhance cell loss and/or dysfunction. By identifying new genes involved in cellular degeneration, we will be able to clarify the role of alpha-synuclein in causing disease and identify specific therapeutic avenues to pursue. A secondary goal of this research is to elucidate the cellular mechanisms that are used by neurons to fight against degeneration and to find ways to enhance these mechanisms to combat disease.