The Role of Palmitoylation in the Pathogenesis of Huntington Disease

Huntington disease (HD), is an adult-onset progressive, degenerative disease affecting the neurons of a particular area of the brain called the striatum. The striatum is partially responsible for regulating movement, and HD affects the part of the striatum responsible for inhibiting unwanted movement. The primary symptom of HD is chorea, or involuntary “”dance-like”” movements. Currently, no effective treatment or cures exist, and death occurs on average 15 years after disease onset. HD is caused by a mutation in the Huntington gene where a short sequence at the beginning of the gene is multiplied, resulting in more than 36 repetitions. The mutation is inherited, so that people with HD have a 50 percent chance of passing it onto their children. The mutation has many effects on the function of the Huntington protein (htt), including interfering with how it interacts with other proteins, such as Huntington Interacting Protein 14 (HIP14). HIP14 is a “”PAT”” enzyme, which is a type of enzyme involved in a process called palmitoylation. There is a growing body of evidence to suggest that palmitoylation plays an important role in HD. Shaun Sanders’ research into HD involves the development of a new, genetically modified “conditional knockout” mouse model. Using this model, Sanders can “”turn off”” HIP14 when and where wanted, in a particular organ or area of an organ, like turning a light off in one room but not in another. He will then look for the symptoms of HD in the mouse model. His research will provide more evidence for the role of HIP14 in HD and further validate the model of palmitoylation in HD. The results will also improve our knowledge regarding “”PAT”” enzymes and palmitoylation which will expand the understanding of other neurological diseases, such as Schizophrenia and mental retardation.