THE clumps of defective protein long assumed to kill brain cells in people with Huntington鈥檚 disease actually help these cells survive.
Huntington鈥檚 disease is triggered by mutations in a protein called huntingtin, causing it to aggregate and eventually form large, insoluble clumps within cells. The conventional view is that these clumps kills cells, but they might also be a harmless side effect or even a protective mechanism. 鈥淭he possibilities kept me up at night,鈥� says Steve Finkbeiner of the University of California, San Francisco.
So his team developed a sophisticated method, involving genetic engineering and computer-driven microscopes, for tracking the life and death of individual rat neurons with the mutated protein. The results were clear: neurons in which clumps appear survive longer (Nature, vol 431, p 805).
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鈥淭his is a seminal paper,鈥� says Harry Orr, who studies brain diseases at the University of Minnesota in Minneapolis. 鈥淚t compromises one of the major theories of how huntingtin causes disease.鈥� The results suggests that smaller, soluble clumps of huntingtin 鈥� which combine to form the larger clumps 鈥� may be the true culprits behind the disease, he says.
The findings, if they apply to human cells as well, could affect the hunt for a treatment. Researchers are looking for drugs that stop the huntingtin protein clumping together. 鈥淏ut one prediction of ours is that some of these drugs could actually make the disease worse,鈥� Finkbeiner says.
His team鈥檚 cell-tracking method might also help reveal the role of the protein clumps and tangles characteristic of related diseases such as Alzheimer鈥檚.