| Huntington disease (HD) is a neurodegenerative disorder characterized by motor and cognitive symptoms. In HD patients, the protein huntingtin contains an abnormal expansion of a polyglutamine tract, which leads to the selective dysfunction and death of striatal and cortical neurons. Among other cellular dysfunctions, cholesterol and ganglioside GM1 synthesis are affected in HD neurons.;In this thesis I demonstrated that impaired cholesterol metabolism in HD cells results from aberrant interaction of mutant huntingtin with the transcription factor Sterol Regulatory Element-Binding Protein 2 (SREBP2). I also showed that administration of GM1 restores normal motor behavior in HD mice.;My studies have led to a better understanding of the causes of cholesterol metabolism dysregulation in HD, and have identified GM1 as a potential therapy for the disease. |
