Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Duke chemists isolating individual molecules of toxic protein in Alzheimer’s, Parkinson’s disease

17.03.2005


To understand the formation of the brain-clogging deposits that cause such disorders as Alzheimer’s and Parkinson’s diseases, Duke University chemists have figured out how to capture and "micromanipulate" the single molecular building blocks of the deposits.



Their aim is to understand the detailed assembly process for the toxic protein called amyloid plaque. Such basic understanding, they said, could lead to approaches to preventing plaque formation.

The researchers led by Boris Akhremitchev are using the infinitesimal tip of a customized atomic force microscope (AFM) to capture, isolate and study single molecules, called monomers, that are the building blocks of the toxic protein polymers known as amyloid fibrils. Atomic force microscopes use a sharp microscopic tip to image surfaces and detect energy differences by mechanically probing molecular surfaces.


In a poster presentation at the American Chemical Society’s annual meeting, the researchers will describe the first biophysical analysis of interactions between monomers that form the amyloid fibrils associated with Parkinson’s disease.

This presentation will include studies by Chad Ray, a graduate student in Akhremitchev’s research group, that clarify the nature of binding forces between amyloid molecules. The poster session will take place March 16, 2005, 7:30 - 10 p.m. Pacific Standard Time, in Hall D of the San Diego Convention Center.

This work was funded by the Camille and Henry Dreyfus Foundation and by Duke University.

It has been difficult to study the chemistry of formation of these fibrils within the brains of humans and other animals, said Akhremitchev, who is an assistant professor of chemistry.

In the brain, "monomers of all kinds are suspended in a soup in equilibrium," he said. Given that the components of amyloid fibrils measure only billionths of a meter and are floating in a disordered mix, "the initial stages of amyloid aggregation are not fully understood," he said.

"When you start a normal reaction, molecules are free in solution so they interact with each other randomly," Akhremitchev said. "If you want to dissect the process, you would rather want to study interactions individually."

Thus, the Duke chemists capture individual monomers at the end of long chained polyethylene glycol molecules. They then attach one such tethered monomer to a microscope slide and the other to the AFM microscope tip. They can then bring the isolated and suspended molecules together to study how and whether they interact.

The Duke researchers study these interactions by retracting the tip of their AFM, which can measure changes in force at the atomic scale. Pulling back the tip can induce a measurable tug on the chemical bonds that hold together the two elevated monomers.

By pulling on such bonds, the Duke scientists can deduce how much energy was required to bring the molecules together. Then, using their knowledge of protein chemistry, they can develop hypotheses about how those particular monomers might, or might not, be involved in the evolution of fibrils, They can thus develop a better understanding of amyloid aggregation.

The scientists are also seeking the precise point during fibril formation when interactions between monomers become irreversible. Defining that point is important because "the fibrils are virtually indestructible once formed," he said.

"How all these monomers interact to form these amyloid fibrils is just not known at this point," said Akhremitchev. "And that is why it is such a great challenge. That’s what we want to learn."

Monte Basgall | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>