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 Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>