Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse gene suppresses Alzheimer's plaques and tangles

13.11.2009
Protein reduces levels of amyloid beta and tau hyperphosphorylation, 2 hallmarks of Alzheimer's

Investigators at Burnham Institute for Medical Research (Burnham) and colleagues have identified a novel mouse gene (Rps23r1) that reduces the accumulation of two toxic proteins that are major players in Alzheimer's disease: amyloid beta and tau.

The amyloid and tau lowering functions of this gene were demonstrated in both human and mouse cells. Amyloid beta is responsible for the plaques found in the brains of Alzheimer's patients. Tau causes the tangles found within patients' brain cells. The study was published in the journal Neuron on November 12. These findings could lead to new treatments for Alzheimer's disease.

Scientists throughout the world are searching for ways to reduce the levels of these two proteins as a means of treating Alzheimer's, so finding a gene that can control the amount of both proteins is particularly important. Overproduction of amyloid beta and its accumulation within senile plaques in the brain and the formation of abnormal tau tangles (neurofibrillary tangles composed of hyperphosphorylated tau protein) are major causes of disrupted brain function in Alzheimer's disease.

Hauxi Xu, Ph.D., professor and acting director of the Neurodegenerative Disease Research program at Burnham, collaborated with Nobel laureate Paul Greengard, Ph.D., of the Laboratory of Molecular and Cellular Neuroscience at The Rockefeller University, Stanley Cohen, Ph.D., of the Department of Genetics at Stanford University School of Medicine, Limin Li, Ph.D., of Functional Genetics, Inc., and with researchers from Xiamen University, to demonstrate that the RPS23R1 protein, which is encoded by the gene, triggers a signaling pathway within brain cells that inhibits a protein called GSK-3 (glycogen synthase kinase-3), which regulates both amyloid beta generation and tau phosphorylation (required for tangle formation).

The team also found that the Rps23r1 gene, whose human counterpart has not yet been identified, was created through a process called retroposition, in which a gene is duplicated through the reverse transcription (or reading) of mRNA and the duplicate is placed in a different location in the cell's DNA. Although most retroposition events result in non-functional duplicates (called pseudogenes) , in rare cases, retroposed genes, like Rps23r1, can become functional.

"From the point of view of treating Alzheimer's disease, if we can express the mouse gene in human brain cells, we may be able to control the buildup of amyloid beta and tau neurofibrillary tangles," said Dr. Xu. "From an evolutionary point of view, we have found an example of a retroposed gene that took on a completely new function."

Dr. Xu and colleagues used a technology called random homozygous gene perturbation to search for genes that regulate amyloid beta generation. This allowed the team to identify the Rps23r1 gene and found that the RPS23R1 protein it encodes can interact with a protein called adenylate cyclase that stimulates a second protein called protein kinase A, which inhibits GSK-3 activity. The effects of RPS23R1 on reducing amyloid beta levels and tau phosphorylation were corroborated in a transgenic Alzheimer's disease mouse model. The team subsequently determined that Rps23r1 is a reverse-transcribed version of the mouse ribosomal protein S23 (Rps23) gene, which is nearly identical to the human Rps23 gene.

About Burnham Institute for Medical Research

Burnham Institute for Medical Research is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The institute ranks among the top four institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. For the past decade (1999-2009), Burnham ranked first worldwide in the fields of biology and biochemistry for the impact of its research publications (defined by citations per publication), according to the Institute for Scientific Information.

Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit public benefit corporation.

Josh Baxt | EurekAlert!
Further information:
http://www.burnham.org

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>