Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme action creates protein linked to Alzheimer’s disease

12.08.2005


Researchers at UT Southwestern Medical Center have defined a key step in the production of beta-amyloid, a short protein that is thought to be responsible for the development of Alzheimer’s disease. Understanding this step may aid in the discovery of drugs that could help block the disease from developing.



In Alzheimer’s disease, too much beta-amyloid is produced by an enzyme that has many other essential roles. As a result, simply blocking the whole enzyme knocks out many of its other functions - which is fatal to the organism.

Using cultured human and mouse cells, as well as test-tube assays, UT Southwestern researchers singled out how just one portion of the enzyme, a protein called nicastrin, is involved in the pathway that produces beta-amyloid, thereby leading to Alzheimer’s disease. They hope next to work on ways to specifically block nicastrin. The study appears in the August 12 issue of the journal Cell.


"The work provides an attractive potential strategy for developing treatment for Alzheimer’s disease," said Dr. Gang Yu, assistant professor in the Center for Basic Neuroscience and of cell biology and senior author of the study. The research uncovered an "unprecedented mechanism of biochemistry," Dr. Yu said.

Nicastrin is a large protein that is a component of an enzyme called gamma-secretase, which is lodged in the cell’s membrane. When it is at the cell surface, nicastrin sticks out into the area outside the cell. It has been thought to play a key role in the creation of a protein called amyloid-beta - the prime suspect for the damage Alzheimer’s does to the brain - but the exact mechanism was unknown.

Dr. Yu and his colleagues found that nicastrin binds to several proteins lodged in the cell’s membrane, including one called amyloid precursor protein, or APP. Nicastrin then guides membrane-bound proteins to the active area of gamma-secretase, which then splits the proteins. APP, for example, is chopped into two parts: amyloid-beta, which is then shipped to the outside of the cell, and another part that remains inside. Amyloid-beta forms the plaques seen in brains afflicted with Alzheimer’s.

"Actually, it’s quite a simple mechanism," Dr. Yu said. "Hopefully, we can screen for compounds that can block this process and find the exact pathways and how it can be regulated in Alzheimer’s disease."

Now that nicastrin’s function has been ascertained, it opens a way to block just the splitting of APP, leaving all the enzyme’s other functions intact. For instance, it may be possible to generate chemical compounds that specifically prevent nicastrin from latching on to APP. If APP doesn’t attach to nicastrin, APP remains intact and harmless. Meanwhile, nicastrin would be free to bind all the other essential proteins that it works on.

"We want to find a particular way to block the recognition of APP but not the others," Dr. Yu said.

UT Southwestern researchers in the Center for Basic Neuroscience involved in the study were Sanjiv Shah, lead author and student research assistant; Drs. Sheu-Fen Lee and Katsuhiko Tabuchi, assistant instructors; Drs. Yi-Heng Hao and Cong Yu, postdoctoral researchers; and Dr. Thomas Südhof, director of the center. Other UT Southwestern researchers were Quincey LaPlant, Medical Scientist Training Program student; Dr. Charles E. Dann III, postdoctoral researcher in biochemistry; and Dr. Haydn Ball, assistant professor of biochemistry.

The study was supported by the National Institutes of Health, the Welch Foundation, the American Health Assistance Foundation, the American Federation for Aging Research and the Alzheimer’s Association.

Aline McKenzie | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>