Fatal cellular malfunction identified in Huntington's disease

June 23, 2014 by Michael C. Purdy
Fatal cellular malfunction identified in Huntington's disease
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. Credit: Robert Boston

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.

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 . 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 . 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 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 , which also produce the mutated .

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 , also known as Lou Gehrig's , have been linked to problems with . Scientists may be able to build upon these new findings to better understand these disorders.

Explore further: Study shows for first time how Huntington's disease protein could cause death of neurons

More information: 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.

Related Stories

Study shows for first time how Huntington's disease protein could cause death of neurons

May 19, 2014
(Medical Xpress)—Scientists at the University of Pittsburgh School of Medicine have identified for the first time a key molecular mechanism by which the abnormal protein found in Huntington's disease can cause brain cell ...

Novel RNAi therapy silences mutated Huntington's disease gene and reduces symptoms

May 21, 2014
A targeted gene silencing strategy blocks production of the dysfunctional huntingtin (Htt) protein, the cause of Huntington's disease, a fatal, inherited neurodegenerative disorder. The effectiveness of this RNA interference ...

Molecular 'scaffold' could hold key to new dementia treatments

June 3, 2014
Researchers at King's College London have discovered how a molecular 'scaffold' which allows key parts of cells to interact, comes apart in dementia and motor neuron disease, revealing a potential new target for drug discovery.

Stem cells overcome damage in other cells by exporting mitochondria

January 16, 2014
A research team has identified a protein that increases the transfer of mitochondria from mesenchymal stem cells to lung cells. In work published in The EMBO Journal, the researchers reveal that the delivery of mitochondria ...

Breakthrough on Huntington's disease

May 23, 2013
Researchers at Lund University have succeeded in preventing very early symptoms of Huntington's disease, depression and anxiety, by deactivating the mutated huntingtin protein in the brains of mice.

New therapeutic target identified for Huntington's disease

November 26, 2013
A new study published 26th November in the open access journal PLOS Biology, identifies a new target in the search for therapeutic interventions for Huntington's disease – a devastating late-onset neurodegenerative disorder.

Recommended for you

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

New study reveals contrasts in how groups of neurons function during decision making

July 19, 2017
By training mice to perform a sound identification task in a virtual reality maze, researchers at Harvard Medical School and the Istituto Italiano di Tecnologia (IIT) have identified striking contrasts in how groups of neurons ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.