Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UIC chemists characterize Alzheimer’s plaque precursor

23.11.2005


Using a nuclear magnetic resonance technique, University of Illinois at Chicago chemists have obtained the first molecular-level images of precursors of bundled fibrils that form the brain plaques seen in Alzheimer’s disease.



Untangling the molecular structure of these pre-fibril forms, which may be the key neurotoxins in Alzheimer’s, may help identify targets for new drugs to combat many neurodegenerative diseases.

Microscopic bundled fibrils made of proteins called amyloid-beta are presumed to be the toxic culprits in the senile plaques found in the brain with Alzheimer’s. But there is increasing evidence that even smaller assemblies of amyloid-beta found prior to formation of pre-fibrils are the real nerve-killers. Scientists have been frustrated that electron microscope images of these nanometer-scale spherical assemblies have failed to reveal any distinct molecular structure.


Yoshitaka Ishii, assistant professor of chemistry at UIC, and graduate student Sandra Chimon have now determined this structure using a methodology developed with high-resolution solid-state nuclear magnetic resonance, or SSNMR. Details were reported in a Communication article last month in JACS, the Journal of the American Chemical Society.

"This is the first case showing that these intermediate species, the smaller assemblies, have a well-defined structure," said Ishii, who conducted a two-year search to map the structure of the pre-fibril assemblies, then spent another year confirming his findings.

Ishii’s technique uses what is called time-resolution SSNMR to view nanoscale spectral images of this chemical formation.

Thioflavin, a dye commonly used to stain amyloid senile plaques, is applied to detect formation of the intermediate assemblies in florescence. The intermediate sample is then frozen to capture quickly changing spectral images of the molecules before they can self-assemble into fibril-forming sheets.

The resulting SSNMR "snapshots" provide a structural diagram for finding molecular binding targets that may stop proteins from misfolding, which may stop Alzheimer’s disease from developing.

"We’re interested in how the molecules assemble in this shape, and eventually into fibrils," Ishii said. "We wanted to find out what kind of structure each amino acid takes in a certain site of a protein at the atomic level. It gives us an idea of how these molecules interact with each other to make this structure."

Ishii said the SSNMR technique may be used to study small chemical subunits involved in diseases such as Parkinson’s and prion diseases like mad cow or Creutzfeld-Jacob, to name just some of the 20 or so neurodegenerative diseases characterized by misfolding proteins.

"You want to design molecules that will interact and prevent this," said Ishii. "That’s been difficult. Now we have a new clue to learn how."

Paul Francuch | EurekAlert!
Further information:
http://www.uic.edu

More articles from Life Sciences:

nachricht Repairing damaged hearts with self-healing heart cells
22.08.2017 | National University Health System

nachricht Biochemical 'fingerprints' reveal diabetes progression
22.08.2017 | Umea University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Cholesterol-lowering drugs may fight infectious disease

22.08.2017 | Health and Medicine

Meter-sized single-crystal graphene growth becomes possible

22.08.2017 | Materials Sciences

Repairing damaged hearts with self-healing heart cells

22.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>