Navigation Links
Novel role of protein in generating amyloid-beta peptide
Date:4/27/2009

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."


'/>"/>

Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related medicine news :

1. Novel cancer drug reduces neuroblastoma growth by 75 percent
2. Porter Novelli Begins Work With NHLBI on COPD Awareness Effort
3. Ethicon Endo-Surgery Novel Investigational Notes and SSL Devices Featured in 15 Presentations at Sages
4. Singapore First in Southeast Asia to Use Novel Treatment for Sports and Musculoskeletal Injuries
5. Mount Sinai researchers discover novel mechanisms that might causally link type-2 diabetes to Alzheimers disease
6. A Decision Beyond Life and Death: Novel Examines Effects of Controversial Procedure on Patients, Their Families and Doctors
7. Weight Watchers(R) Expands Licensed Food Categories with Launch of New Baked Goods, Frozen Novelty and Cheese Products to Encourage a More Sensible Lifestyle
8. Glissandra Skincare Inc. Launches Website Showcasing New and Novel Anti-Aging Skincare Products
9. AFRAID TO GO HOME, A Novel About Violence Against Women, Released By Tristan/Isolde Publishing
10. Endo Licenses Novel Pain Therapy from Grunenthal
11. Derma Sciences Gains FDA Clearance for Novel BIOGUARD(TM) Barrier Dressing with NIMBUS(R) Technology
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/18/2017)... ... January 18, 2017 , ... Park ... financial planning services to families and business owners in the greater Kansas City ... children with developmental disabilities. , The Lakemary Center is a comprehensive educational resource ...
(Date:1/18/2017)... ... 18, 2017 , ... Michael J. Hennessy Associates, Inc., (MJH), ... for Biosimilars, announced Michael J. Hennessy Associates, Inc. President Michael J. Hennessy, Jr. ... through thought leader interaction in, live video and interactive digital platforms. , In ...
(Date:1/18/2017)... ... January 18, 2017 , ... Floundering on New Year’s resolutions? Need an excuse ... for a reset. The U.S. Apple Association agrees and recommends starting each day ... that contribute to heart disease. , The U.S. Apple Association – which represents apple ...
(Date:1/17/2017)... California (PRWEB) , ... January 17, 2017 , ... ... have a point of difference. Eden Activewear is a stand-out company for several ... are exclusively online and only manufacture on demand, this is called 'Agile' manufacturing ...
(Date:1/17/2017)... ... January 17, 2017 , ... SunView Software’s Service Smart Technology has ... the Year. , Each year, Pink Elephant recognizes a new product or ... address a specific business problem or opportunity. The award highlights original innovations that were ...
Breaking Medicine News(10 mins):
(Date:1/18/2017)... GREENWOOD VILLAGE, Colo. , Jan. 18, 2017 /PRNewswire/ ... an independent chain of pharmacies based in ... Safe Rx™ Locking Prescription Vials (LPVs) in selected Good Day ... abuse now have a cost-effective alternative for secure storage," ... Safe Rx.  "For less than the price of a ...
(Date:1/18/2017)... SAN ANTONIO , Jan. 18, 2017   ... the process of diagnosing breast cancer through the development ... appointment of Steve Miller as SVP of ... of Product Realization at FUJIFILM SonoSite, with headquarters in ... dedicated the majority of his 30-year career to the ...
(Date:1/18/2017)... Ximbio, a non-profit online one-stop-shop for the global life ... North American headquarters in Kendall Square, Cambridge, Massachusetts ... ... in October 2014 as a business unit of UK- based ... foundation Cancer Research UK. Ximbio.com allows scientists to ...
Breaking Medicine Technology: