Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

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

ORNL
Transmission electron microscopy demonstrates the fibrillar nature of huntingtin aggregates.
ORNL
Transmission electron microscopy demonstrates the fibrillar nature of huntingtin aggregates.

Abstract:
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.

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

Oak Ridge, TN | Posted on May 19th, 2011

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.

####

About Oak Ridge National Laboratory
ORNL is managed by UT-Battelle for the Department of Energy’s Office of Science.

For more information, please click here

Contacts:
Bill Cabage
ORNL Communications
(865) 574-4399

Copyright © Newswise

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

Laboratories

Freeze-dried foam soaks up carbon dioxide: Rice University scientists lead effort to make novel 3-D material August 16th, 2017

News and information

Freeze-dried foam soaks up carbon dioxide: Rice University scientists lead effort to make novel 3-D material August 16th, 2017

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Two Scientists Receive Grants to Develop New Materials: Chad Mirkin and Monica Olvera de la Cruz recognized by Sherman Fairchild Foundation August 16th, 2017

Scientists from the University of Manchester and Diamond Light Source work with Deben to develop and test a new compression stage to study irradiated graphite at elevated temperatures August 15th, 2017

Imaging

Industry’s First Dedicated Cryo-DualBeam System Automates Preparation of Frozen, Biological Samples: New Thermo Scientific Aquilos FIB/SEM protects sample integrity and enhances productivity for cryo-electron tomography workflow August 8th, 2017

Thermo Fisher Scientific Advances Cryo-EM Leadership to Drive Structural Biology Discoveries: New Thermo Scientific Krios G3i raises bar for performance, automation and time-to-results Breakthrough Thermo Scientific Glacios provides a cryo-EM entry path for a broader range of res August 8th, 2017

New Quattro Field Emission ESEM Emphasizes Versatility and Ease of Use: Thermo Scientific Quattro ESEM allows materials science researchers to study nanoscale structure in almost any material under a range of environmental conditions August 8th, 2017

Thermo Fisher Scientific’s New Talos F200i S/TEM Delivers Flexible, High-Performance Imaging: New compact S/TEM can be configured to meet specific imaging and analytical requirements for materials characterization in research laboratories August 8th, 2017

Govt.-Legislation/Regulation/Funding/Policy

Freeze-dried foam soaks up carbon dioxide: Rice University scientists lead effort to make novel 3-D material August 16th, 2017

2-faced 2-D material is a first at Rice: Rice University materials scientists create flat sandwich of sulfur, molybdenum and selenium August 14th, 2017

Engineers pioneer platinum shell formation process – and achieve first-ever observation August 11th, 2017

Moving at the Speed of Light: University of Arizona selected for high-impact, industrial demonstration of new integrated photonic cryogenic datalink for focal plane arrays: Program is major milestone for AIM Photonics August 10th, 2017

Nanomedicine

Freeze-dried foam soaks up carbon dioxide: Rice University scientists lead effort to make novel 3-D material August 16th, 2017

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Two Scientists Receive Grants to Develop New Materials: Chad Mirkin and Monica Olvera de la Cruz recognized by Sherman Fairchild Foundation August 16th, 2017

JPK reports on how the University of Glasgow is using their NanoWizard® AFM and CellHesion module to study how cells interact with their surroundings August 2nd, 2017

Discoveries

Freeze-dried foam soaks up carbon dioxide: Rice University scientists lead effort to make novel 3-D material August 16th, 2017

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Fewer defects from a 2-D approach August 15th, 2017

Scientists from the University of Manchester and Diamond Light Source work with Deben to develop and test a new compression stage to study irradiated graphite at elevated temperatures August 15th, 2017

Announcements

Freeze-dried foam soaks up carbon dioxide: Rice University scientists lead effort to make novel 3-D material August 16th, 2017

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Two Scientists Receive Grants to Develop New Materials: Chad Mirkin and Monica Olvera de la Cruz recognized by Sherman Fairchild Foundation August 16th, 2017

Scientists from the University of Manchester and Diamond Light Source work with Deben to develop and test a new compression stage to study irradiated graphite at elevated temperatures August 15th, 2017

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project