Navigation Links
ORNL, UTGSM study compares structures of Huntington's disease protein

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.


Contact: Morgan McCorkle
DOE/Oak Ridge National Laboratory

Related medicine news :

1. Worm study provides hope for deadly disease of the brain
2. Surgery Soon After Stroke Can Be Risky: Study
3. Stroke Rates Declining Among Seniors, Study Shows
4. Study Warns of Kidney Damage Risk with Popular Mesothelioma Drug, Reports Surviving Mesothelioma
5. Genes May Raise Risk of Cerebral Palsy, Study Finds
6. Transparency lacking in clinical trials, BU study finds
7. Study: Body Dysmorphic Disorder patients have higher risk of personal and appearance-based rejection sensitivity
8. Home Blood Pressure Monitoring Likely Saves Money, Study Finds
9. Kids From Dairy Farms Have Lower Allergy Risk, Study Finds
10. BUSM study: Obesity may be impacted by stress
11. Graphic Cigarette-Label Warnings Work, Study Finds
Post Your Comments:
Related Image:
ORNL, UTGSM study compares structures of Huntington's disease protein
(Date:6/26/2016)... ... June 26, 2016 , ... On June 10-11, 2016, A Forever Recovery, ... Festival and World’s Longest Breakfast Table in Battle Creek, MI, where the rehabilitation facility ... home to some of the world’s leading providers of cereal and other breakfast foods. ...
(Date:6/26/2016)... Charlotte, NC (PRWEB) , ... June 26, 2016 , ... Brent Kasmer, a legally blind ... able to be personalized through a fitness app. The fitness app plans to fix the ... solutions currently only offer a one size fits all type program , They ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... Austin residents ... the American College of Mohs Surgery and to Dr. Russell Peckham for medical and ... highly effective treatment for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room , the ... Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. , “We ... new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, ... Bronze Wellness at Work award to iHire in recognition of their exemplary accomplishments in ... the 7th annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott in ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... 2016 Jazz Pharmaceuticals plc (Nasdaq: ... Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended ("HSR"), ... Inc. ("Celator"; Nasdaq: CPXX ) expired effective ... As previously announced on May 31, 2016, ... agreement under which Jazz Pharmaceuticals has commenced a tender ...
(Date:6/24/2016)... Calif. , June 24, 2016  Global ... a biopharmaceutical company developing novel therapeutics for the ... needs, today announced the closing of its previously ... common stock, at the public offering price of ... the offering were offered by GBT. GBT estimates ...
(Date:6/24/2016)... 2016 Dehaier Medical Systems Ltd. (NASDAQ: ... markets and sells medical devices and wearable sleep respiratory ... strategic cooperation agreement with Hongyuan Supply Chain Management Co., ... June 20, 2016, to develop Dehaier,s new Internet medical ... Dehaier will leverage Hongyuan Supply Chain,s sales platform to ...
Breaking Medicine Technology: