The Role of SOD1 in a Drosophila Model of Spinocerebellar Ataxia 3 (Machado-Joseph's Disease). Christopher Acquafredda, John Warrick. University of Richmond, Richmond, VA.

   Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD), is a dominantly inherited human ataxia caused by an unstable CAG repeat on human chromosome 14q32.1. Research has been done that shows the overexpression of Superoxidative Dismutase 1 (SOD1), which naturally reduces free radicals in the cytoplasm, increases the lifespan of flies up to 40%, suggesting SOD1 and its effects on oxidative stress are important factors in aging and lifespan determination. Based on this, we propose that adding additional copies of SOD1 into the genome of the Drosophila by the use of GAL4/UAS system with a driver targeted to the photoreceptor, that the progression of MJD will be slowed and may show a rescued phenotype. Also, down regulation of SOD1 will be detrimental to fly aging and will cause a quicker progression of MJD due to an increase in ROS. We assessed the degeneration using semi thin plastic sections of fly eyes and light microscopy. Our data suggest influencing the expression of SOD1 in fly eyes with neurodegeneration caused by MJD had little effect. Other work in our lab altering SOD2 levels showed different results. SOD2 is expressed in the mitochondria. This suggests a specific link between mitochondrial and cytoplasmic SOD levels and neurodegeneration.