(Press-News.org) OAK RIDGE, Tenn., July 16, 2014 -- Neutron scattering research at the Department of Energy's Oak Ridge National Laboratory has revealed clear structural differences in the normal and pathological forms of a protein involved in Huntington's disease.
Huntington's disease, an incurable neurodegenerative disorder, starts as a genetic mutation that leads to an overabundance of "huntingtin" protein fragments, which form clumps in the brain.
Valerie Berthelier of the University of Tennessee Graduate School of Medicine, who co-led the study published in Biophysical Journal with ORNL's Chris Stanley, said the goal was to establish a baseline understanding of huntingtin's structure in order to eventually determine the true structural basis of Huntington's disease.
"This is a very first step -- the hope is that we do this basic research to shed light on the structures of the protein," Berthelier said. "If we can start identifying any of these structures as toxic or potentially toxic, and then think about how drugs could interact with them, then we might be getting to the point of rationally designing therapeutics that would target those specific structures."
The researchers conducted a side-by-side study of model protein systems in solution using a time-resolved small-angle neutron scattering technique at ORNL's High Flux Isotope Reactor. The use of neutrons, a non-damaging but highly penetrating particle, allowed the team to study the biological materials over time without degrading the samples' structural integrity.
"We compared the normal and disease versions of the protein to see how they change over time," Stanley said. "You can see there's a discrepancy all the way from the early stages to the end-state fibrils."
The study's results showed key differences in the ways mutant and normal huntingtin proteins take shape. The disease protein, for instance, initially forms aggregates of one to two peptides, whereas the normal version makes bigger aggregates, gathering seven or eight peptides together.
These data on the very early stages of protein aggregate formation support a growing focus of the research in the amyloid field. Amyloid disorders, such as Parkinson's, Alzheimer's and Huntington's, all involve protein aggregation phenomena leading to a disease.
"There is no strong correlation between neuronal cell loss and the amount of protein aggregates found in the brain," Stanley said. "You could have a case with a lot of aggregates but minimal symptoms -- and you can find the converse. Researchers think there must be something happening at the earliest stage that's giving rise to toxicity."
Stanley says the team hopes to continue its research to obtain higher-resolution structural data and refine their understanding of the huntingtin protein.
"We'd like to use this small-angle neutron scattering technique in combination with others to get a better idea for how these early structures are forming and also ask the question -- are they toxic or not?" Stanley said.
INFORMATION:
The research is published as "Investigating the Structural Impact of the Glutamine Repeat in Huntingtin Assembly." Coauthors are Helen McWilliams-Koeppen, Erica Rowe and Tatiana Perevozchikova.
HFIR is DOE Office of Science user facility. ORNL's Center for Structural Molecular Biology is also supported by DOE's Office of Science. The research on Huntington's Disease was supported in part by the Physicians' Medical Education and Research Foundation at UT Medical Center and by the National Institutes of Health.
UT-Battelle manages ORNL for the Department of Energy's Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit http://science.energy.gov/.
Image: http://www.ornl.gov/Image%20Library/Main%20Nav/ORNL/News/News%20Releases/2014/huntington_highres.jpg?code=4b3c6575-d679-483e-8138-ca69cff08ece
Cutline: Researchers used neutron scattering experiments to clarify structural differences between the normal (left) and pathological (right) forms of huntingtin protein aggregates. The pathological form of this protein is implicated in Huntington's disease.
NOTE TO EDITORS: You may read other press releases from Oak Ridge National Laboratory or learn more about the lab at http://www.ornl.gov/news. Additional information about ORNL is available at the sites below:
Twitter - http://twitter.com/oakridgelabnews
RSS Feeds - http://www.ornl.gov/ornlhome/rss_feeds.shtml
Flickr - http://www.flickr.com/photos/oakridgelab
YouTube - http://www.youtube.com/user/OakRidgeNationalLab
LinkedIn - http://www.linkedin.com/companies/oak-ridge-national-laboratory
Facebook - http://www.facebook.com/Oak.Ridge.National.Laboratory
ORNL, UTGSM study compares structures of Huntington's disease protein
2014-07-16
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
Expert guidance on hand hygiene in healthcare settings
2014-07-16
CHICAGO (July 16, 2014) – Expert guidance released today offers updated evidence reviews and recommendations for hand hygiene in healthcare facilities. The guidance is featured in the August issue of Infection Control and Hospital Epidemiology and emphasizes best practices for implementing and optimizing hand hygiene programs to prevent the spread of healthcare-associated infections (HAIs). The guidance is part of the Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates produced in a collaborative effort led by the Society ...
Drug's effect on Alzheimer's may depend on severity of disease
2014-07-16
A cancer drug that has shown promise against Alzheimer's disease in mice and has begun early clinical trials has yielded perplexing results in a novel mouse model of AD that mimics the genetics and pathology of the human disease more closely than any other animal model.
The drug, bexarotene, was found to reduce levels of the neurotoxic protein amyloid-beta in experimental mice with late-stage Alzheimer's but to increase levels during early stages of disease.
The finding, by researchers at the University of Illinois at Chicago College of Medicine, was reported July 16 ...
Research connects pregnancy loss and cardiovascular disease
2014-07-16
The Annals of Family Medicine today published an article detailing research showing that women with a history of pregnancy loss are at higher risk for cardiovascular disease later in adulthood than other women, work completed by physicians in the Center for Primary Care and Prevention (CPCP) at Memorial Hospital of Rhode Island.
The article "Risk of Cardiovascular Disease Among Postmenopausal Women with Prior Pregnancy Loss: The Women's Health Initiative" stems from the analysis of data from the maternity experiences of a sample of 77,701 women, according to Donna Parker, ...
Dispersant from Deepwater Horizon spill found to persist in the environment
2014-07-16
The 2010 Deepwater Horizon (DWH) spill in the Gulf of Mexico was the largest accidental release of oil into the ocean, with approximately 210 million gallons gushing from the blown out well. In an attempt to prevent vast quantities of oil from fouling beaches and marshes, BP applied 1.84 million gallons of chemical dispersant to oil to oil released in the subsurface and to oil slicks at the sea surface. The dispersant was thought to rapidly degrade in the environment.
A new study by scientists at Haverford College and Woods Hole Oceanographic Institution (WHOI) has found ...
Researchers develop EHR algorithms to identify undiagnosed hypertension
2014-07-16
CHICAGO – A new study authored by Northwestern Medicine® researchers found that reviewing electronic health records (EHRs) using algorithms can successfully identify patients with previously undiagnosed hypertension, or high blood pressure, with a high rate of accuracy. Of the 1,033 patients that were identified with the EHR algorithms and evaluated, 361 were formally diagnosed with the hypertension and 290 others were diagnosed with related blood pressure conditions such as prehypertension, white-coat hypertension or elevated blood pressure. The study, "A Technology-Based ...
Worm study provides hope for deadly disease of the brain
2014-07-16
LIVERPOOL, UK – 17 July 2014: An untreatable and deadly neurodegenerative disease has been modelled and treated in worms by University of Liverpool researchers, suggesting a cure could be found for humans.
The scientists studied adult onset neuronal lipofuscinosis (ANCL) which usually strikes around 1 in 100,000 people in Europe and North America in their 30s and results in death by the mid-40s. There is currently no known treatment for this disease, though it has recently been identified as being caused by mutations in the gene called DNAJC5.
For the first time scientists, ...
Cholesterol-lowering drugs may reduce cardiovascular death in Type 2 diabetes
2014-07-16
WINSTON-SALEM, N.C. – July 16, 2014 – Heart disease and stroke are the leading causes of death and disability among people with Type 2 diabetes. In fact, at least 65 percent of people with diabetes die from some form of heart disease or stroke, according to the American Heart Association.
However, a new study by researchers at Wake Forest Baptist Medical Center suggests that the use of cholesterol-lowering statins may help prolong the lives of people with diabetic cardiovascular disease.
The study is published in the current online edition of Diabetes Care.
"Although ...
Recommendations prioritize strategies to prevent ventilator-associated pneumonia
2014-07-16
CHICAGO (July 16, 2014) – Thousands of critically ill patients on life support develop ventilator-associated pneumonia (VAP) each year. A new document released today by a consortium of professional organizations helps prioritize strategies to prevent this potentially fatal infection.
This guidance, featured in the update of the Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals, is published in the August issue of Infection Control and Hospital Epidemiology and was produced in a collaborative effort led by the Society for Healthcare ...
Business groups, capital market participation have complementary effects for Indian companies
2014-07-16
HOUSTON – (July 16, 2014) – Being a part of a business group and participating in capital markets can have a significant positive impact on an Indian company's performance in the stock market, according to a new study on Indian entrepreneurship by emerging-economy experts at Rice University, the Indian School of Business in Hyderabad, India, and the graduate business school INSEAD Singapore.
The findings contradict prior research that suggests business groups in developing economies act mainly as substitutes to poorly developed economic institutions in these countries. ...
Does practice really make perfect?
2014-07-16
Does practice really make perfect? It's an age-old question, and a new study from Rice University, Princeton University and Michigan State University finds that while practice won't make you perfect, it will usually make you better at what you're practicing.
"This question is the subject of a long-running debate in psychology," said Fred Oswald, professor and chair of psychology at Rice and one of the study's co-authors. "Why do so few people who are involved in sports such as golf, musical instruments such as the violin or careers such as law or medicine ever reach an ...