Project 458196

Huntington's disease (HD) is a hereditary and currently incurable neurodegenerative disease that is caused by accumulation of a toxic protein called mutant huntingtin in neurons. Gangliosides are lipids that are abundant in the healthy brain and are important for proper communication between cells and to maintain overall brain health. In HD and other neurodegenerative diseases, levels of a particular ganglioside, GM1, are reduced. If GM1 is administered to mouse models, it reverses all their disease symptoms and reduces the accumulation of the toxic mutant huntingtin from the brain. I will investigate how GM1 treatment results in this lowering of mutant huntingtin. I will measure how GM1 promotes the removal of mutant huntingtin from neurons and how GM1 can strengthen the ability of brain immune cells to dispose of the toxic protein. In doing so, my studies may help to determine how GM1 can be used as a therapeutic in the clinic to treat patients suffering from Huntington's disease and other diseases where toxic proteins accumulate in the brain, including Parkinson's and Alzheimer's disease.