Featured Research

from universities, journals, and other organizations

Structures of Huntington's disease protein compared in study

Date:
July 16, 2014
Source:
DOE/Oak Ridge National Laboratory
Summary:
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. Neutron scattering research has revealed clear structural differences in the normal and pathological forms of a protein involved in Huntington's disease.

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.
Credit: Image courtesy of DOE/Oak Ridge National Laboratory

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.

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.


Story Source:

The above story is based on materials provided by DOE/Oak Ridge National Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Tatiana Perevozchikova, ChristopherB. Stanley, HelenP. McWilliams-Koeppen, EricaL. Rowe, Valerie Berthelier. Investigating the Structural Impact of the Glutamine Repeat in Huntingtin Assembly. Biophysical Journal, 2014; 107 (2): 411 DOI: 10.1016/j.bpj.2014.06.002

Cite This Page:

DOE/Oak Ridge National Laboratory. "Structures of Huntington's disease protein compared in study." ScienceDaily. ScienceDaily, 16 July 2014. <www.sciencedaily.com/releases/2014/07/140716112809.htm>.
DOE/Oak Ridge National Laboratory. (2014, July 16). Structures of Huntington's disease protein compared in study. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2014/07/140716112809.htm
DOE/Oak Ridge National Laboratory. "Structures of Huntington's disease protein compared in study." ScienceDaily. www.sciencedaily.com/releases/2014/07/140716112809.htm (accessed September 2, 2014).

Share This




More Mind & Brain News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
Coffee Then Napping: The (New) Key To Alertness

Coffee Then Napping: The (New) Key To Alertness

Newsy (Aug. 30, 2014) Researchers say having a cup of coffee then taking a nap is more effective than a nap or coffee alone. Video provided by Newsy
Powered by NewsLook.com
Young Entrepreneurs Get $100,000, If They Quit School

Young Entrepreneurs Get $100,000, If They Quit School

AFP (Aug. 29, 2014) Twenty college-age students are getting 100,000 dollars from a Silicon Valley leader and a chance to live in San Francisco in order to work on the start-up project of their dreams, but they have to quit school first. Duration: 02:20 Video provided by AFP
Powered by NewsLook.com
Baby Babbling Might Lead To Faster Language Development

Baby Babbling Might Lead To Faster Language Development

Newsy (Aug. 29, 2014) A new study suggests babies develop language skills more quickly if their parents imitate the babies' sounds and expressions and talk to them often. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins