Researchers have shed light on how the deadly Huntington's disease affects the brain by discovering that the disease causes a dramatic accumulation of cholesterol in the brain.
"Cholesterol is essential for promoting the connection network among brain cells and in maintaining their membrane integrity. Both the level of cholesterol and its delivery to the proper locations in the cell are essential for the survival of neurons," explains Mayo Clinic molecular biologist Cynthia McMurrary, Ph.D.
"Our discovery that a mutant Huntington's disease protein derails the cholesterol delivery system and causes cholesterol accumulation in neurons provides us with key results and solid clues to the mechanism of this disease," says Dr. McMurray. "Fully understanding the mechanism of toxicity is the key to developing treatments."
Huntington's disease — also known as Huntington's chorea and St. Vitus's dance — is a degenerative condition that causes nerve cells in the brain to waste away. Symptoms include uncontrolled movements, emotional disturbances and mental deterioration.
The mutant protein of Huntington's attacks the railroad system of brain cells and impairs transport of essential materials required for neurons to function. When this transportation system goes awry in the parts of the brain affected in Huntington's disease, motor skills, cognitive skills and even speech can be affected. A person cannot move without shaking, and physical control gradually deteriorates, often accompanied by personality changes, depression and increased risk of suicide.
Approximately 30,000 Americans have Huntington's disease. Another 150,000 carry the gene and have a 50 percent risk of passing it on to their children. The disease is easily diagnosed by a blood test but symptoms usually don't appear until middle age.
Published as the cover story of the December 2006 issue of Human Molecular Genetics, these findings, say the researchers, provide the first direct link between the Huntington's protein and the protein that controls capture and trafficking inside the cell. Their research suggests a possible means by which Huntington's disease functions.