Featured Research

from universities, journals, and other organizations

Novel Role Of Protein In Generating Amyloid-beta Peptide

Date:
May 3, 2009
Source:
University of California - San Diego
Summary:
A defining hallmark of Alzheimer's disease is the accumulation of the amyloid-beta protein, otherwise known as "senile plaques," in the brain's cortex and hippocampus, where memory consolidation occurs. Researchers have identified a novel protein which, when over-expressed, leads to a dramatic increase in the generation of the amyloid-beta protein.

A defining hallmark of Alzheimer's disease is the accumulation of the amyloid β protein (Aβ), 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 Aβ.

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 Aβ is derived when the amyloid precursor protein (APP) is "cut" by two enzymes, β-secretase (or BACE) and γ-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 Aβ 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 Aβ generation, and the scientists narrowed this segment down to a 37-amino-acid stretch that can lead to changes in Aβ.

"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 Aβ 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 Aβ. To test this, the scientists knocked out RANBP9 in the cell, and discovered that 60% less Aβ 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.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University of California - San Diego. "Novel Role Of Protein In Generating Amyloid-beta Peptide." ScienceDaily. ScienceDaily, 3 May 2009. <www.sciencedaily.com/releases/2009/04/090427193240.htm>.
University of California - San Diego. (2009, May 3). Novel Role Of Protein In Generating Amyloid-beta Peptide. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2009/04/090427193240.htm
University of California - San Diego. "Novel Role Of Protein In Generating Amyloid-beta Peptide." ScienceDaily. www.sciencedaily.com/releases/2009/04/090427193240.htm (accessed September 30, 2014).

Share This



More Mind & Brain News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Do Video Games Trump Brain Training For Cognitive Boosts?

Do Video Games Trump Brain Training For Cognitive Boosts?

Newsy (Sep. 29, 2014) More and more studies are showing positive benefits to playing video games, but the jury is still out on brain training programs. Video provided by Newsy
Powered by NewsLook.com
Your Spouse's Personality May Influence Your Earnings

Your Spouse's Personality May Influence Your Earnings

Newsy (Sep. 26, 2014) Research from Washington University suggest people with conscientious spouses have greater career success. Video provided by Newsy
Powered by NewsLook.com
Can A Blood Test Predict Psychosis Risk?

Can A Blood Test Predict Psychosis Risk?

Newsy (Sep. 26, 2014) Researchers say certain markers in the blood can predict risk of psychosis later in the life. The test can aid in early treatment for the condition. Video provided by Newsy
Powered by NewsLook.com
Harpist Soothes Gorillas, Orangutans With Music

Harpist Soothes Gorillas, Orangutans With Music

AP (Sep. 25, 2014) Teri Tacheny, a harpist, has a loyal following of fans who appreciate her soothing music. Every month, gorillas, orangutans and monkeys amble down to hear her play at the Como Park Zoo in Minnesota. (Sept. 25) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins