Huntington’s disease, HD, is an incurable, hereditary brain disorder. Nerve cells become damaged, causing various parts of the brain to deteriorate. The disease affects movement, behavior and cognition – the affected individual’s abilities to walk, think, reason, and talk are gradually eroded to such a point that they eventually become entirely reliant on other people for care. HD has a major emotional, mental, social and economic impact on the lives of the patients as well as their friends and family.
It used to be called Huntington’s Chorea, because the involuntary movements made by patients with the disease can appear to be like jerky dancing – “Chorea” comes form the Greek word choreia meaning “dancing”. This disease affects both men and women equally. According to the Department of Health, UK, there are about 6,000 people in the UK with the disease. The Huntington’s Society of America says 1 in every 10,000 Americans have the disease- about 30,000 people. It is estimated that at least 150,000 other Americans have a 50% risk of developing HD. Prevalence of the disease varies according to ethnic ancestry. People with Asian or African inheritance have a 1 in 1,000,000 risk of becoming affected, while the risk for Caucasian people is 70 to 100 times higher. Huntington's disease, which afflicted the folksinger Woody Guthrie, is a fatal, inherited neurodegenerative disorder. The faulty gene that causes HD is found on chromosome number 4. Huntington's disease results from a gene mutation that leads to a defective form of the huntingtin protein (htt). The mutation is dominant, meaning that a child of an affected parent has a 50 percent chance of inheriting Huntington's. "Studies have shown that Huntington's disease occurs in part because the mutated huntingtin protein accumulates within cells and is toxic to them," said Ana Maria Cuervo, M.D., Ph.D. "In our investigation of how the accumulating huntingtin protein affects the functioning of cells, we found that it interferes with the cells' ability to digest and recycle their contents." All cells rely on several different mechanisms to break down "old" proteins and other components and recycle them. Collectively known as autophagy (literally, "self-eating"), these processes keep cells clean and uncluttered and provide them with replacement parts that will function better. After studying two mouse models of Huntington's disease as well as lymphoblasts (white cells) from people with the disease, she and her team found that the mutated huntingtin protein was sabotaging the cell's garbage-collecting efforts. Using state of the art technology, Dr Danny Hatters and his colleagues at the University of Melbourne's Department of Biochemistry and Molecular Biology at the Bio 21 Institute observed how human mutant 'huntingtin' proteins form into large clumps, which kills brain cells and leads to progressed Huntington's disease. While researchers previously thought that small clusters of the mutant protein kept accumulating over time until they overwhelmed and killed the brain cells, Dr Hatters' team found that these clusters were static, which means they form in a more unpredictable manner than previously thought. The discovery reveals the clusters place a steady stress on cells over time rather than steadily building up over time to some critical "toxic" level as previously thought. "Why it takes so long for the cells to die in human disease is not known - however it could be that cells eventually cannot compensate anymore from the process where toxicity is built up to form one cluster called oligomers," he says. "Given the predominant neurological signs and striking neuronal death in HD, most studies on htt function have focused on adult neurons," explains Dr. Sandrine Humbert from the Institut Curie in Orsay, France. "However, although htt is not restricted to differentiated neurons and is found at high levels in dividing cells, no studies have investigated a possible role for htt...
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