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HD is a hereditary disorder caused by a mutated form of the protein Huntingtin. Patients experience a loss of motor and cognitive function, ultimately leading to death.
The CauseHuntington's Disease (HD) results from a mutation in the protein Huntingtin. This protein contains a segment where the amino acid glutamine is repeated several times. This is called the polyglutamine region. In most individuals, the polyglutamine region contains somewhere between ten and thirty-four repeats. However, in people suffering from Huntington's the protein will contain thirty-five repeats or more. The number of times the amino acid is repeated correlates to the severity of this disease. People with thirty-five to thirty-nine repeats may experience few or no symptoms over the course of their lifetime. Almost everyone whose polyglutamine region contains forty or more repeats will suffer from the disease if they reach a late enough age, with onset occurring around an average of forty-years-old. Individuals with fifty-five or more repeats may begin showing symptoms as a juvenile. The disease is usually fatal between ten and twenty years after symptoms first appear. The pathology of Huntington's Disease is not yet fully understood, but what is known is that when Huntingtin proteins contain too many repeats, they bind more readily to each other and to other important proteins that contain polyglutamine regions. The extra repeats also impair the natural function of Huntingtin. Brains of HD patients display clumps of Huntingtin protein called aggresomes, but they appear to be an artifact of neuronal cell death and not the cause. It appears more likely that free floating mutant Huntingtin binds to other polyglutamine containing factors in the cell's nucleus meant to interact with DNA and direct the cell on how to function, grow, and divide. Mutant Huntingtin can also cause errors in the cells' ability to create energy through their mitochondria. As a result, the mutant Huntingtin interferes with neuronal function over time and leads to the death and dysfunction of cells in the brain. SymptomsHuntington's Disease is characterized by three types of symptoms: motor, psychiatric, and cognitive. Motor dysfunction involves involuntary, uncontrolled movements. These can begin as minor twitches and tics, but eventually lead to a general loss of coordination and balance that make walking, speaking, and eating increasingly difficult. Psychiatric symptoms are harder to diagnose, with the most common symptom being depression. This can include hostility and a loss of motivation. Many patients also become manic-depressive and experience strong mood swings. Delusions and hallucinations also sometimes result from the disease and can frequently cause the subject to suffer from feelings of paranoia. Cognitive impairment can be widespread, especially approaching the end stages of the disease. Simple tasks such as mathematics and routine chores can become a challenge as memory and decision-making become impaired. Often, the loss creates difficultly distinguishing these symptoms from those of a psychiatric nature. Reasons for HopeAnimal models of HD have been studied for years and have provided many targets for treatment. Ceasing the production of mutant Huntingtin and inhibiting the action of protein cleaving enzymes named caspases both seem to have the potential to halt or reverse the action of disease. References:1. Young, A. B. (2003) J. Clin. Invest. 111, 299-302. 2. Nguyen, T., Hamby, A., and Massa, S. M. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 11840–11845
The copyright of the article What is Huntington's Disease in Huntington's Disease is owned by Daniel Devine. Permission to republish What is Huntington's Disease in print or online must be granted by the author in writing.
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