Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Natural Plant Compound Prevents Alzheimer's Disease in Mice

29.01.2014
A daily dose of the antioxidant fisetin keeps mice----even those with genetic mutations linked to Alzheimer's----from experiencing memory and learning deficits as they age.

A chemical that's found in fruits and vegetables from strawberries to cucumbers appears to stop memory loss that accompanies Alzheimer's disease in mice, scientists at the Salk Institute for Biological Studies have discovered.

In experiments on mice that normally develop Alzheimer's symptoms less than a year after birth, a daily dose of the compound----a flavonol called fisetin----prevented the progressive memory and learning impairments.

The drug, however, did not alter the formation of amyloid plaques in the brain, accumulations of proteins which are commonly blamed for Alzheimer's disease. The new finding suggests a way to treat Alzheimer's symptoms independently of targeting amyloid plaques.

"We had already shown that in normal animals, fisetin can improve memory," says Pamela Maher, a senior staff scientist in Salk's Cellular Neurobiology Laboratory who led the new study. "What we showed here is that it also can have an effect on animals prone to Alzheimer's."

More than a decade ago, Maher discovered that fisetin helps protect neurons in the brain from the effects of aging. She and her colleagues have since----in both isolated cell cultures and mouse studies----probed how the compound has both antioxidant and anti-inflammatory effects on cells in the brain. Most recently, they found that fisetin turns on a cellular pathway known to be involved in memory.

"What we realized is that fisetin has a number of properties that we thought might be beneficial when it comes to Alzheimer's," says Maher.

So Maher----who works with Dave Schubert, the head of the Cellular Neurobiology Lab----turned to a strain of mice that have mutations in two genes linked to Alzheimer's disease. The researchers took a subset of these mice and, when they were only three months old, began adding fisetin to their food. As the mice aged, the researchers tested their memory and learning skills with water mazes. By nine months of age, mice that hadn't received fisetin began performing more poorly in the mazes. Mice that had gotten a daily dose of the compound, however, performed as well as normal mice, at both nine months and a year old.

"Even as the disease would have been progressing, the fisetin was able to continue preventing symptoms," Maher says.

In collaboration with scientists at the University of California, San Diego, Maher's team next tested the levels of different molecules in the brains of mice that had received doses of fisetin and those that hadn't. In mice with Alzheimer's symptoms, they found, pathways involved in cellular inflammation were turned on. In the animals that had taken fisetin, those pathways were dampened and anti-inflammatory molecules were present instead. One protein in particular----known as p35----was blocked from being cleaved into a shorter version when fisetin was taken. The shortened version of p35 is known to turn on and off many other molecular pathways. The results were published December 17, 2013, in the journal Aging Cell.

Studies on isolated tissue had hinted that fisetin might also decrease the number of amyloid plaques in Alzheimer's affected brains. However, that observation didn't hold up in the mice studies. "Fisetin didn't affect the plaques," says Maher. "It seems to act on other pathways that haven't been seriously investigated in the past as therapeutic targets."

Next, Maher's team hopes to understand more of the molecular details on how fisetin affects memory, including whether there are targets other than p35.

"It may be that compounds like this that have more than one target are most effective at treating Alzheimer's disease," says Maher, "because it's a complex disease where there are a lot of things going wrong."

They also aim to develop new studies to look at how the timing of fisetin doses affect its influence on Alzheimer's.

"The model that we used here was a preventive model," explains Maher. "We started the mice on the drugs before they had any memory loss. But obviously human patients don't go to the doctor until they are already having memory problems." So the next step in moving the discovery toward the clinic, she says, is to test whether fisetin can reverse declines in memory once they have already appeared.

Other researchers on the paper were Antonio Currais, Marguerite Prior, Richard Dargusch, Jennifer Ehren, and David Schubert of the Salk Institute and Aaron Armando and Oswald Quehenberger of the University of California at San Diego.

The work was supported by grants from the Alzheimer's Association, Paul Slavik, the National Institutes of Health, the Alzheimer's Drug Discovery Foundation, and the George E. Hewitt Foundation.

About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

Chris Emery | Newswise
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Why some neurons “outsource” their cell body
21.04.2015 | Nationales Bernstein Netzwerk Computational Neuroscience

nachricht Bubbles dilemma solved after more than twenty years
21.04.2015 | University of Twente

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: On the trail of a trace gas

Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.

In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...

Im Focus: Advances in Molecular Electronics: Lights On – Molecule On

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and the University of Konstanz are working on storing and processing information on the level of single molecules to create the smallest possible components that will combine autonomously to form a circuit. As recently reported in the academic journal Advanced Science, the researchers can switch on the current flow through a single molecule for the first time with the help of light.

Dr. Artur Erbe, physicist at the HZDR, is convinced that in the future molecular electronics will open the door for novel and increasingly smaller – while also...

Im Focus: Pruning of Blood Vessels: Cells Can Fuse With Themselves

Cells of the vascular system of vertebrates can fuse with themselves. This process, which occurs when a blood vessel is no longer necessary and pruned, has now been described on the cellular level by Prof. Markus Affolter from the Biozentrum of the University of Basel. The findings of this study have been published in the journal “PLoS Biology”.

The vascular system is the supply network of the human organism and delivers oxygen and nutrients to the last corners of the body. So far, research on the...

Im Focus: Astronomers reveal supermassive black hole's intense magnetic field

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a supermassive black hole in a distant galaxy

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a...

Im Focus: A “pin ball machine” for atoms and photons

A team of physicists from MPQ, Caltech, and ICFO proposes the combination of nano-photonics with ultracold atoms for simulating quantum many-body systems and creating new states of matter.

Ultracold atoms in the so-called optical lattices, that are generated by crosswise superposition of laser beams, have been proven to be one of the most...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

World Conference On Regenerative Medicine 2015: Registration And Abstract Submission Now Open

25.03.2015 | Event News

University presidents from all over the world meet in Hamburg

19.03.2015 | Event News

 
Latest News

Better battery imaging paves way for renewable energy future

21.04.2015 | Materials Sciences

Extending climate predictability beyond El Niño

21.04.2015 | Earth Sciences

Risk Perception: Social Exchange Can Amplify Subjective Fears

21.04.2015 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>