Huntington's Disease

The brain is a complex organ with numerous connections and interconnections that both aid in its study and confound it. Because of the intricate network of connections between brain cells, a disease that leads to degeneration of a specific population of brain cells can have a drastic effect on the brain as well as on the patient as a whole. There are many examples of neurological disorders; one prominent example is Huntington's disease (HD).

Within the brain, there are regions that control specific facets of brain function. For example, there is a region where all somatosensory information is ultimately processed, and another region where smells are processed. There is also a brain region that sends a signal to initiate body movement. Many brain functions integrate information from various brain regions. Movement is one such example. A major brain region that has important feedback on movement is the basal ganglia. The basal ganglia is itself made up of several distinct brain regions. The two most common disorders of the basal ganglia are Parkinson's disease (PD) and Huntington's disease. A person affected with PD will not be able to move as much as a healthy person, whereas someone with HD will exhibit excess, uncontrolled movements. A characteristic movement is a ballismus, or large forceful movement that usually occurs in the arms.

The brain is composed of two main types of cells, neurons and glia. Neurons are cells that send electrical [Page 870]signals within the brain or down to the spinal cord. Glia are the support cells. Within the neurons, there are multiple subtypes. One such subtype is called the medium spiny neurons. They are medium in size, relative to other neurons, and have spiny-appearing projections from the cell body by which they send and receive electrical signals. Medium spiny neurons reside in the basal ganglia, and these cells degenerate in HD. Along with movement disorders, HD can cause intellectual degeneration as well as emotional disorders.

There is currently no known treatment or cure for HD. The only medications used can alleviate some movement or emotional problems. Research is focused on the genetic cause of HD, which is a mutation in the huntingtin gene. This gene encodes the huntingtin protein, which as of yet has no known effect in brain cells. The type of mutation in the huntingtin gene is called a trinucleotide repeat expansion. When DNA encodes a protein, every three nucleotides of the coding DNA stand for one particular amino acid to be added to the protein.

Certain rare arrangements of nucleotides make a gene prone to trinucleotide repeat expansion, or abnormal multiple repeats of the trinucleotide segment. In HD, the trinucleotide repeat occurs in the coding region of the huntingtin gene; therefore, the resulting protein has an excessive string of one amino acid within the central region of the protein, resulting in a mutant protein of altered shape and size which can no longer function as normal. In the case of huntingtin, the mutated protein takes on a new toxic function, unrelated to the normal protein's function. The excess amino acid is glutamine.

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