Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Neutrons Provide First Sub-Nanoscale Snapshots of Huntington’s Disease Protein

20.05.2011
Researchers at the Department of Energy’s Oak Ridge National Laboratory and the University of Tennessee have for the first time successfully characterized the earliest structural formation of the disease type of the protein that causes Huntington’s disease. The incurable, hereditary neurological disorder is always fatal and affects one in 10,000 Americans.

Huntington’s disease is caused by a renegade protein “huntingtin” that destroys neurons in areas of the brain concerned with the emotions, intellect and movement. All humans have the normal huntingtin protein, which is known to be essential to human life, although its true biological functions remain unclear.

Christopher Stanley, a Shull Fellow in the Neutron Scattering Science Division at ORNL, and Valerie Berthelier, a UT Graduate School of Medicine researcher who studies protein folding and misfolding in Huntington’s, have used a small-angle neutron scattering instrument, called Bio-SANS, at ORNL’s High Flux Isotope Reactor to explore the earliest aggregate species of the protein that are believed to be the most toxic.

Stanley and Berthelier, in research published today in Biophysical Journal, were able to determine the size and mass of the mutant protein structures¯from the earliest small, spherical precursor species composed of two (dimers) and three (trimers) peptides¯along the aggregation pathway to the development of the resulting, later-stage fibrils. They were also able to see inside the later-stage fibrils and determine their internal structure, which provides additional insight into how the peptides aggregate.

“Bio-SANS is a great instrument for taking time-resolved snapshots. You can look at how this stuff changes as a function of time and be able to catch the structures at the earliest of times,” Stanley said. “When you study several of these types of systems with different glutamines or different conditions, you begin to learn more and more about the nature of these aggregates and how they begin forming.”

Normal huntingtin contains a region of 10 to 20 glutamine amino acids in succession. However, the DNA of Huntington’s disease patients encodes for 37 or more glutamines, causing instability in huntingtin fragments that contain this abnormally long glutamine repeat. Consequentially, the mutant protein fragment cannot be degraded normally and instead forms deposits of fibrils in neurons.

Those deposits, or clumps, were originally seen as the cause of the devastation that ensues in the brain. More recently researchers think the clumping may actually be a kind of biological housecleaning, an attempt by the brain cells to clean out these toxic proteins from places where they are destructive. Stanley and Berthelier set out to learn through neutron scattering what the toxic proteins were and when and where they occurred.

At the HFIR Bio-SANS instrument, the neutron beam comes through a series of mirrors that focus it on the sample. The neutrons interact with the sample, providing data on its atomic structure, and then the neutrons scatter, to be picked up by a detector. From the data the detector sends of the scattering pattern, researchers can deduce at a scale of less than billionths of a meter the size and shape of the diseased, aggregating protein, at each time-step along its growth pathway.

SANS was able to distinguish the small peptide aggregates in the sample solution from the rapidly forming and growing larger aggregates that are simultaneously present. In separate experiments, they were able to monitor the disappearance of the single peptides, as well as the formation of the mature fibrils.

Now that they know the structures, the hope is to develop drugs that can counteract the toxic properties in the early stages, or dissuade them from taking the path to toxicity. “The next step would be, let’s take drug molecules and see how they can interact and affect these structures,” Stanley said.

For now, the researchers believes Bio-SANS will be useful in the further study of Huntington’s disease aggregates and applicable for the study of other protein aggregation processes, such as those involved in Alzheimer’s and Parkinson’s diseases.

“That is the future hope. Right now, we feel like we are making a positive contribution towards that goal,” Stanley said.

The research was supported by the National Institutes of Health. HFIR and Bio-SANS are supported by the DOE Office of Science.

ORNL is managed by UT-Battelle for the Department of Energy’s Office of Science.

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

Bill Cabage | Newswise Science News
Further information:
http://www.ornl.gov

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Superconducting vortices quantize ordinary metal

Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.

These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Rapid water formation in diffuse interstellar clouds

25.06.2018 | Physics and Astronomy

Using tree-fall patterns to calculate tornado wind speed

25.06.2018 | Earth Sciences

'Stealth' material hides hot objects from infrared eyes

25.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>