How Huntington's disease kills brain cells

In a discovery that could open new opportunities for treating Huntington's disease, researchers claimed they have learned how mutations in the gene that causes the fatal disorder kill brain cells.

Lead author Hiroko Yano of Washington University School of Medicine in St. Louis found in mice and in mouse brain cell cultures that the disease impairs the transfer of proteins to energy-making factories inside brain cells.

The factories, known as mitochondria, need these proteins to maintain their function. When disruption of the supply line disables the mitochondria, brain cells die.

"We showed the problem could be fixed by making cells overproduce the proteins that make this transfer possible," said Yano.

"We don't know if this will work in humans, but it's exciting to have a solid new lead on how this condition kills brain cells," he added.

Huntington's symptoms, which typically begin in the middle-age, include involuntary jerking movements, disrupted coordination and cognitive problems such as dementia.

Drugs cannot slow or stop the progressive decline caused by the disorder, which leaves patients unable to walk, talk or eat.

Huntington's disease is caused by a defect in the gene that makes the Huntingtin protein.

Scientists have known for some time that the mutated form of the Huntingtin protein impairs mitochondria and that this disruption kills brain cells.

But they have had difficulties in understanding specifically how the gene harms the mitochondria.

Yano and her colleagues found that the mutated Huntingtin protein binds to a group of proteins called TIM23.

This protein complex normally helps transfer essential proteins and other supplies to the mitochondria.

The researchers discovered that the mutated Huntingtin protein impairs that process.

The findings were published online in Nature Neuroscience.