Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel role of protein in generating amyloid-beta peptide

29.04.2009
A defining hallmark of Alzheimer's disease is the accumulation of the amyloid â protein (Aâ), otherwise known as "senile plaques," in the brain's cortex and hippocampus, where memory consolidation occurs.

Researchers at the University of California, San Diego School of Medicine have identified a novel protein which, when over-expressed, leads to a dramatic increase in the generation of Aâ.

Their findings, which indicate a potential new target to block the accumulation of amyloid plaque in the brain, will be published in the May 1 issue of the Journal of Biological Chemistry.

"The role of the multi-domain protein, RANBP9, suggests a possible new therapeutic target for Alzheimer's disease," said David E. Kang, PhD, assistant professor of neurosciences at UC San Diego and director of this study.

The neurotoxic protein Aâ is derived when the amyloid precursor protein (APP) is "cut" by two enzymes, â-secretase (or BACE) and ã-secretase (or Presenilin complex.) However, inhibiting these enzymes in order to stop the amyloid cascade has many negative side effects, as these enzymes also have various beneficial uses in brain cells. So the researchers looked for an alternative way to block the production of amyloid beta.

In order for cleavage to occur, the APP needs to travel to cholesterol-enriched sites within the cell membrane called RAFTS, where APP interacts with the two enzymes. It is this contact that the researchers sought to block.

Kang explains that the researchers identified the RANBP9 protein by studying low density lipoprotein receptor-related protein (LRP), a protein that rapidly shuttles Aâ out of the brain and across the blood-brain barrier to the body, where it breaks down into harmless waste products. A small segment of LRP can also stimulate Aâ generation, and the scientists narrowed this segment down to a 37-amino-acid stretch that can lead to changes in Aâ.

"RANBP9 is one of the proteins we identified that interacted with this LRP segment, but one that had never before been associated with disease-related neuronal changes," said Kang. "We discovered that this protein interacts with three components involved in Aâ generation – LRP, APP and BACE1 – and appears to 'scaffold' them into a structure."

Kang explained that these three components must come together to result in the first cut or cleaving that leads to production of Aâ. To test this, the scientists knocked out RANBP9 in the cell, and discovered that 60% less Aâ was produced.

"This unique factor enhances the production of beta amyloid," said Kang. "Inhibiting the RANBP9 protein may offer an alternative approach to therapy, by preventing contact between APP and the enzyme that makes the cut essential to produce amyloid plaques." The researchers' next step is to verify these findings in animal models.

According to the Alzheimer's Association, an estimated 5.3 million people have Alzheimer's disease in the United States alone, and a new case is diagnosed every seven seconds.

Madepalli K. Lakshmana, Ph.D., the study's first author, added that "this study is the first to identify RANBP9 as a target to potentially inhibit the movement of APP to RAFTS so that amyloid beta peptide generation can be prevented. As such, a small molecule drug that can reduce the RANBP9 protein levels could offer an effective treatment for Alzheimer's disease."

Additional contributors to the study include Il-Sang Yoon, Eunice Chen and Edward H. Koo, of UC San Diego Department of Neurosciences; and Elizabetta Bianchi from the Institut Pasteur in Paris.

This work was supported in part by the American Health Assistance Foundation, the Alzheimer's Association, and the National Institutes of Health, National Institute on Aging.

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

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 Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>