Huntington Disease

Throughout human history scientists wondered what a disease is, and how they can prevent it. There are different types of diseases. Some diseases are spread by microbes and viruses, and some are genetic, also called disorders. Genetic disorder is a disease that is caused by an abnormality in one’s DNA. The abnormality, such as mutation, may occur in the single gene as well as in the whole chromosome or in a set of chromosomes. [9] One of the genetic disorders that greatly influence human life is Huntington Disease. Huntington Disease (HD), also called Huntington Chorea, is a brain disorder resulted from a gene mutation in protein called huntingtin. The mutation in huntingtin causes a progressive degeneration of the neurons in the basal ganglia. The word “chorea” comes from Greek, and means “dance” in Latin. It refers to the uncontrollable movements of the afflicted individual. Even though the disorder is named after George Huntington, he was not the first scientist who witnessed this disease. His famous paper “On Chorea”, which was submitted by him in 1872, was the first paper that described Chorea in details. Much of the information for Huntington’s paper was drawn from his father’s and grandfather’s written observations, both physicians who had described the involuntary shaking in patients. The paper gained Huntington instant notability because he was able to clearly point to the genetic inheritance as the mode of transmission, and he also noticed that the first symptoms usually appear in the adult age and are accompanied by a mental decline as well. It is due to these significant observations and conclusions that “Huntington’s Disease” bears George Huntington’s name. [6] Nowadays, approximately 30,000 people in the United States suffer from HD, with another 15,000 at risk of developing this disorder. It is also known that the onset of the symptoms of HD is usually between the ages of 30 and 50; although in 10% of cases, the onset of the disorder is developed in the late childhood or early adolescence. [3]

Basal ganglia (See Figure 1) are the structures in the human brain, affected by the huntingtin protein, and both basal ganglia and huntingtin protein have to function properly for the human organism to be healthy. For many years, basal ganglia were described in anatomy courses as strictly motor structures. However, recent research shows that they are involved in most areas of cognitive and emotional functioning. Basal ganglia also play an important role in human learning, particularly sequence learning and category learning. “Sequence learning is learning a relative sequence of events across time. It’s vital for all aspects of human functioning, including a sequencing of component movements in complex motor plans (e.g., dance), sequencing of grammatical elements in language, and sequencing of subgoals in complex reasoning (e.g., mental arithmetic).” Category learning is a “learning to categorize stimuli and associate them with appropriate responses is an important human capacity. It underlies our ability to choose appropriately (e.g., choose foods categorized as safe but avoid those categorized as poisonous) and to perform abstract inferences (e.g., if a particular food is categorized as poisonous, then a similar food may also be poisonous and should be avoided).” [5] Basal ganglia are crucial for the human body, but for them to work normally huntingtin protein should function properly.

The reason for malfunction of basal ganglia is a mutant huntingtin protein. Although the researchers are still investigating huntingtin’s exact purpose, it appears to play a crucial role in nerve cell function. As any other protein, huntingtin (Htt) is contained within an amino acid called glutamine. A person with HD has an exceeded number of glutamines in a particular segment of the protein. These extra glutamines come from having too many copies of the corresponding codon (the one that codes for glutamine) in the chemical code of DNA. The codon has letters C-G-A. People with normally functioning form of huntingtin have from 10 to 35 copies of the C-G-A, when those with 40 or more copies of C-G-A develop HD.[7] “Because glutamine is a polar, or “charged” molecule, the overabundance of glutamine causes links to form within and between proteins.” Htt molecules attach to each other, forming strands that are held together by hydrogen bonds. Rather than forming functional proteins, they develop into knotted, inflexible groupings known as protein aggregates. (See Figure 2) “These fibrous protein aggregates accumulate and interfere with nerve cell function by entrapping key cell regulatory factors.” [1] Located in basal ganglia, nerve cells are affected by mutant huntingtin protein. The aggregates of huntingtin protein cause damage to nerve cells, and when the damage is severe enough, the cells die off. As a result, basal ganglia start to malfunction