Researchers believe they have learned how mutations in the gene that causes Huntington’s disease kill brain cells, a finding that could open new opportunities for treating the fatal disorder. Scientists first linked the gene to the inherited disease more than 20 years ago.
Huntington’s disease affects five to seven people out of every 100,000. Symptoms, which typically begin in 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.
Hiroko Yano, PhD, right, led a team of researchers that learned how the fatal inherited disorder Huntington’s disease kills brain cells. Co-author Albert Kim also is pictured.
Lead author Hiroko Yano, PhD, 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, assistant professor of neurological surgery, neurology and genetics. “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.”
The findings are available online in Nature Neuroscience.
Huntington’s disease is caused by a defect in the huntingtin gene, which makes the huntingtin protein. Life expectancy after initial onset is about 20 years.
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 difficulty understanding specifically how the gene harms the mitochondria.
For the new study, Yano and collaborators at the University of Pittsburgh worked with mice that were genetically modified to simulate the early stages of the disorder.
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 problem seems to be specific to brain cells early in the disease. At the same point in the disease process, the scientists found no evidence of impairment in liver cells, which also produce the mutated huntingtin protein.
The researchers speculated that brain cells might be particularly reliant on their mitochondria to power the production and recycling of the chemical signals they use to transmit information. This reliance could make the cells vulnerable to disruption of the mitochondria.
Other neurodegenerative conditions, including Alzheimer’s disease and amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, have been linked to problems with mitochondria. Scientists may be able to build upon these new findings to better understand these disorders.
Funding from the National Institutes of Health (NIH) (R01 NS039324, R01 NS077748, K01 AG033724), the Huntington’s Disease Society of America (Coalition for the Cure), the Brain & Behavior Research Foundation, and the DSF Charitable Foundation supported this research.
Yano H, Baranov SV, Baranova OV, Kim J, Pan Y, Yablonska S, Carlisle DL, Ferrante RJ, Kim AH, Friedlander RM. Inhibition of mitochondrial protein import by mutant huntingtin. Nature Neuroscience, published online May 18, 2014.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
Michael C. Purdy | Eurek Alert!
Channels for the Supply of Energy
19.11.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
Vine Compound Starves Cancer Cells
19.11.2018 | Julius-Maximilians-Universität Würzburg
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
19.11.2018 | Science Education
19.11.2018 | Ecology, The Environment and Conservation
19.11.2018 | Life Sciences