Grace Baudhuin

Huntington’s disease (HD) is hereditary neurodegenerative disease that causes neuronal breakdown and death. Expanded CAG repeats located in the Huntingtin (HTT) gene cause the gene to encode for mutant huntingtin (mHTT) protein. People with HD can have up to 36 or more CAG repeats, while unaffected individuals have fewer than 27 CAG repeats. The expanded number of repeats leads to huntingtin protein misfolding and aggregation, causing disruptions in normal cell processes of the neuron3. Individuals affected with HD exhibit issues with balance, orientation, and movement, as well as behavioral changes and diminished cognitive performance. Unfortunately, there is no known cure for HD. Two newly discovered compounds, Z218-0041 (GPHR-00353752) and Z218-4418 (GPHR-00353812), from the Gomez-Pastor Laboratory in the Department of Laboratory Medicine and Pathology at the University of Minnesota–Twin Cities have shown to inhibit the function of CK2ɑ’. CK2ɑ’ is involved in the degradation of Heat Shock Factor 1 (HSF1) that degrades protein aggregates. These drugs work as competitive inhibitors to block the activation site of the alpha subunit of the CK2 holoenzyme. The goal of this experiment is to determine how a gradual increase in drug concentration impacts the amount of HSF1 and two of its chaperone proteins, HSP70 and HSP72. We hypothesized that as the concentrations of Z218-0041 and Z218-4418 increase, there will be greater amounts of HSF1 and HSP70/72 in Q111 neuronal cells. By proving the drugs are effective, more studies can be conducted to optimize drug activity and provide some insight on the pathophysiology of HD.