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

News and information

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Journal Nanotechnology Progress International (JONPI) Volume 6, issue 2 coming out soon! December 5th, 2016

Infrared instrumentation leader secures exclusive use of Vantablack coating December 5th, 2016

Construction of practical quantum computers radically simplified: Scientists invent ground-breaking new method that puts quantum computers within reach December 5th, 2016

Imaging

Deep insights from surface reactions: Researchers use Stampede supercomputer to study new chemical sensing methods, desalination and bacterial energy production December 2nd, 2016

Controlled electron pulses November 30th, 2016

Novel silicon etching technique crafts 3-D gradient refractive index micro-optics November 28th, 2016

Scientists shrink electron gun to matchbox size: Terahertz technology has the potential to enable new applications November 25th, 2016

Laboratories

Working under pressure: Diamond micro-anvils with huge pressures will create new materials October 19th, 2016

Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge October 15th, 2016

Scientists Find Static "Stripes" of Electrical Charge in Copper-Oxide Superconductor: Fixed arrangement of charges coexists with material's ability to conduct electricity without resistance October 14th, 2016

Tomoyasu Mani Wins 2016 Blavatnik Regional Award for Young Scientists: Award recognizes his work at Brookhaven Lab to understand the physical processes occurring in organic materials used to harness solar energy October 13th, 2016

Govt.-Legislation/Regulation/Funding/Policy

Construction of practical quantum computers radically simplified: Scientists invent ground-breaking new method that puts quantum computers within reach December 5th, 2016

Shape matters when light meets atom: Mapping the interaction of a single atom with a single photon may inform design of quantum devices December 4th, 2016

Research Study: MetaSOLTM Shatters Solar Panel Efficiency Forecasts with Innovative New Coating: Coating Provides 1.2 Percent Absolute Enhancement to Triple Junction Solar Cells December 2nd, 2016

Deep insights from surface reactions: Researchers use Stampede supercomputer to study new chemical sensing methods, desalination and bacterial energy production December 2nd, 2016

Nanomedicine

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Journal Nanotechnology Progress International (JONPI) Volume 6, issue 2 coming out soon! December 5th, 2016

UTSA study describes new minimally invasive device to treat cancer and other illnesses: Medicine diffusion capsule could locally treat multiple ailments and diseases over several weeks December 3rd, 2016

Nanobiotix Provides Update on Global Development of Lead Product NBTXR3: Seven clinical trials across the world: More than 2/3 of STS patients recruited in the “act.in.sarc” Phase II/III trial: Phase I/II prostate cancer trial now recruiting in the U.S. November 28th, 2016

Discoveries

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Construction of practical quantum computers radically simplified: Scientists invent ground-breaking new method that puts quantum computers within reach December 5th, 2016

Shape matters when light meets atom: Mapping the interaction of a single atom with a single photon may inform design of quantum devices December 4th, 2016

UTSA study describes new minimally invasive device to treat cancer and other illnesses: Medicine diffusion capsule could locally treat multiple ailments and diseases over several weeks December 3rd, 2016

Announcements

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Journal Nanotechnology Progress International (JONPI) Volume 6, issue 2 coming out soon! December 5th, 2016

Infrared instrumentation leader secures exclusive use of Vantablack coating December 5th, 2016

Construction of practical quantum computers radically simplified: Scientists invent ground-breaking new method that puts quantum computers within reach December 5th, 2016

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