Machado-Joseph Disease (MJD) is a human spinocerebellar ataxia caused by a polyglutamine repeat expansion in the Ataxin-3 protein that leads to motor neuron degeneration. The mechanisms by which the toxic ATX3 protein causes degeneration are not yet known. In MJD, the ATX3 protein misfolds, leading to the formation of aggregates. Histone acetyltransferases (HATs) may get trapped in the aggregates, therefore preventing proper regulation of protein acetylation and gene transcription. As a result, neurons may become dysfunctional and die due to transcriptional dysregulation or other dysregulation. The histone acetyltransferase Tip60 functions in neuronal gene control and apoptosis, and elevated levels have been found to rescue axonal transport defects, characterized by locomotive phenotypes, in a Drosophila melanogaster model of Alzheimer’s disease. However, HAT Tip60 has not yet been studied in MJD. Polyglutamine expansions have been associated with axon transport defects. This research investigates the effect of up-regulating and down-regulating HAT Tip60 in a MJD Drosophila melanogaster model to determine how levels of Tip60 expression affect the progression of the disease. This research may lead to an effective target for MJD, Alzheimer Disease, and other neurodegenerative diseases.