The findings are currently in PLoS Computational Biology, an open-access journal published by the Public Library of Science (PloS) in partnership with the International Society for Computational Biology.
These neurodegenerative diseases, including Huntington's disease, share an abnormal deposit of proteins inside nerve cells. This deposition of protein results from a kind of genetic stutter within the cell's nucleus asking for multiple copies of the amino acid glutamine, a building block of protein structure. These disorders are collectively known as polyglutamine diseases. Along with Huntington's, these diseases include spinobulbar muscular atrophy; spinocerebellar ataxia types 1, 2, 3, 6, 7 and 17; and dentatorubral-pallidoluysian atrophy, or Haw River Syndrome.
Haw River Syndrome is a genetic brain disorder first identified in 1998 in five generations of a family having ancestors born in Haw River, N.C. The disorder begins in adolescence (between ages 15 and 30 years) and is characterized by progressive and widespread damage to brain function, leading to loss of coordination, seizures, paranoid delusions, dementia and death within 15 to 20 years.
Scientists are uncertain if protein deposition causes nerve cells to deteriorate and die. However, studies show that the greater the number of glutamine repeats in a protein above a certain threshold, the earlier the onset of disease and the more severe the symptoms. This result suggests that abnormally long glutamine tracts render their host protein toxic to nerve cells.
"Polyglutamine expansion greater than 35 to 40 repeats is definitely a key player in disease etiology and, perhaps, cell death," said Dr. Nikolay V. Dokholyan, assistant professor of biochemistry and biophy
Contact: L.H. Lang
University of North Carolina School of Medicine