Huntington's protein may be kidnapper.
Christopher A. Ross of Johns Hopkins Medical School in Baltimore and his colleagues demonstrated in a test tube how huntingtin contributes to cell death. The scientists were also able to halt the process, saving doomed human cells.
Huntington's disease is a fatal disorder that begins in midlife and eventually destroys muscle control and cognitive abilities. It's caused by a single mutated copy of the gene for huntingtin. The damaged gene makes a version of the protein with an unusually long chain of one of its components, the amino acid glutamine.
Instead of folding into a functional protein, chains of glutamine on the mutant huntingtin molecules stick to each other. These build up in plaques inside brain cells. Similar plaques collect in the brains of people with Alzheimer's disease, but the role of the plaques hasn't yet been determined.
"Surely, it's not good for cells to have glop clogging them up," but the clumps of huntingtin haven't appeared to be directly toxic to cells, says Ross. For example, he notes, the brain cells most likely to die in people with Huntington's disease aren't necessarily the ones containing the protein deposits.
The researchers wondered whether mutant huntingtin proteins might pose indirect harm by binding to short glutamine chains in other proteins in the cell. This would pull important proteins out of service and block their normal function.
One candidate protein for this process is known as CBP, or CREB binding protein, which is central in the biochemistry of cellular survival. The team found that brain samples from people who had died from Huntington's disease, as well as mice with a similar syndrome, had very low amounts of CBP, suggesting that the protein had been sequestered in huntingtin plaques.
The researchers also grew brain cells that produced abnormal huntingtin and found that these also kidnapped CBP. When they added CBP molecules that were missing their strings of glutamine, the molecules didn't collect in deposits and the cells survived.
Now that the researchers have rescued brain cells in laboratory dishes, says Ross, their next task, says Ross, is to do the same in living mice.
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|Date:||Apr 28, 2001|
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