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 Fish recognize their prey by electric colors
13.11.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection
13.11.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection

13.11.2018 | Life Sciences

Fish recognize their prey by electric colors

13.11.2018 | Life Sciences

Ultrasound Connects

13.11.2018 | Awards Funding

VideoLinks
Science & Research
Overview of more VideoLinks >>>