In Huntington's disease, a mutated protein in the body becomes toxic to brain cells. Recent studies have demonstrated that a small region adjacent to the mutated segment plays a major role in the toxicity. Two new studies supported by the National Institutes of Health show that very slight changes to this region can eliminate signs of Huntington's disease in mice.
Researchers do not fully understand why the protein (called mutant huntingtin) is toxic, but one clue is that it accumulates in ordered clumps of fibrils, perhaps clogging up the cells' internal machinery.
"These studies shed light on the structure and biochemistry of the mutant huntingtin protein and on potentially modifiable factors that affect its toxicity," said Margaret Sutherland, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS). "They reveal sites within the huntingtin protein and within broader disease pathways that could serve as targets for drug therapy."
Both studies were published online this week. One study, published in the Journal of Cell Biology, was led by Leslie Thompson, Ph.D., and Joan Steffan, Ph.D., of the University of California, Irvine. The other study, in Neuron, was led by X. William Yang, M.D., Ph.D., of the University of California, Los Angeles in collaboration with Ron Wetzel, Ph.D., of the University of Pittsburgh School of Medicine.
Huntington's disease is inherited, and usually strikes in middle age, producing uncontrollable movements of the legs and arms, a loss of muscle coordination, and changes in personality and intellect. It is inexorably progressive and leads to death of affected persons usually within 20 years after symptoms first appear. Individuals with the disease carry mutations that affect the huntingtin protein. The mutations involve a triple repeat DNA sequence, a type of genetic miscue similarly found in Friedreich's ataxia, Kennedy's disease, fragile X s
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NIH/National Institute of Neurological Disorders and Stroke