Emory University researchers find clue to Huntington's disease mechanism

ATLANTA- Huntington's disease, an inherited progressive neurological disorder, often results in the degeneration of neurons in the hypothalamus, a part of the brain that controls appetite and body weight. Scientists at Emory University School of Medicine have discovered how rogue proteins generated by the genetic mistake present in Huntington's disease poison neurons in the hypothalamus. They demonstrate that the mutant proteins interfere with the function of another protein abundant in the hypothalamus huntingtin-associated protein-1 (HAP1).

The research is published in the July 30 issue of the Journal of Neuroscience. Lead authors are Shi-Hua Li, MD and Xiao-Jiang Li, PhD, faculty members in Emory's Department of Human Genetics, and Zhao-Xue Yu, PhD, postdoctoral fellow. Dr. Chuxia Deng's laboratory at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) also contributed to the study.

Huntington's disease eventually affects many parts of the brain, but the strongest impact is on the basal ganglia, responsible for coordination of movement. Onset usually occurs between 30 and 50 years of age, and the symptoms become progressively worse over the next 15 years. The main symptoms include loss of control of movement, depression and cognitive impairment. Complications include loss of body weight, heart failure and pneumonia. Huntington's occurs at a frequency of five to seven in a hundred thousand, and some relatives of affected individuals have a 50 percent risk of inheriting the responsible mutation responsible. No effective treatment exists.

Huntington's patients suffer from the genetic equivalent of a skipping record or CD In the gene responsible the huntingtin gene the enzymes that copy genetic information get stuck and make additional repeats of the same three-letter sequence CAG. When the number of repeats grows large enough, the property and function of the protein change. The now-expanded region of the pro

Contact: Holly Korschun
Emory University Health Sciences Center

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