Organic plant substance stops Alzheimer's illness in rats

A substance that is found in fruits and vegetables from berries to cucumbers stop memory loss that comes with Alzheimer's illness in rats, scientists have found. In tests on rats that normally develop Alzheimer's illness signs less than a year afterbirth, an everyday dose of the substance -- a flavonol known as fisetin -- avoided the progressive memory and studying problems. The medication, however, did not change forming amyloid plaques in the brain, collections of necessary proteins, which are generally held responsible for Alzheimer's illness.

A substance that is found in fruits and vegetables from berries to cucumbers stop memory loss that comes with Alzheimer's illness in rats, scientists at the Salk Institute for Biological Research have found. In tests on rats that normally create Alzheimer's illness signs less than a season afterbirth, an everyday amount of the substance -- -a flavonol known as fisetin -- -prevented the modern storage and studying problems. The medication, however, did not change developing amyloid plaques in the mind, collections of necessary proteins, which are generally held responsible for Alzheimer's illness. The new finding shows a way to cure Alzheimer's illness symptoms individually of focusing on amyloid plaques.

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

More than a several years ago, Maher found that fisetin helps secure nerves in the mind from the results of getting older. She and her colleagues have since -- -in both separated cell cultures and mouse studies -- -probed how the substance has both antioxidant and anti-inflammatory results on cells in the brain. Most recently, they found that fisetin changes on a cellular pathway known to be engaged in memory.

"What we noticed is that fisetin has various qualities that we thought might be helpful when it comes to Alzheimer's illness," says Maher.

Therefore, Maher -- -who works with Dave Schubert, the head of the Cellular Neurobiology Lab -- -turned to a stress of rats that have mutations in two genes connected to Alzheimer's illness. The researchers took a part of these rats and, when they were only three months old, started including fisetin to their food. As the rats older, the researchers examined their memory and studying skills with water mazes. By nine months of age, rats that did not have fisetin started carrying out more badly in the mazes. Mice that had gotten an everyday dose of the substance, however, conducted as well as normal rats, at both nine months and a year old.

"Even as the illness would have been progressing, the fisetin could continue avoiding symptoms," Maher says.

In cooperation with scientists at the University of California, San Diego, Maher's group next examined the levels of different elements in the brains of rats that had doses of fisetin and those that had not. In rats with Alzheimer's illness signs, they found, routes engaged in cellular inflammation were switched on. In the animals that had taken fisetin, those routes were moistened and anti-inflammatory elements were present instead. 

One proteins in particular -- -known as p35 -- -was obstructed from being cleaved into a smaller version when fisetin was taken. The shortened version of p35 is known to turn on and off many other molecular routes. The results were released December 17, 2013, in the journal Aging Cell.

Studies on separated tissue had suggested that fisetin might also reduce the variety of amyloid plaques in Alzheimer's illness affected brains. However, that statement did not hold up in the rats studies. "Fisetin didn't affect the plaques," says Maher. "It seems to act on other routes that haven't been seriously examined in the past as healing objectives."

Next, Maher's group wishes to understand more of the molecular details on how fisetin affects memory, such as whether there are targets other than p35.

"It may be that substances like this that have more than one target are most effective at dealing with Alzheimer's illness," says Maher, "because it's a complicated illness where there are many things going wrong."

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

"The model that we used here was a precautionary design," describes Maher. "We started the rats 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." Therefore, the next step in moving the finding toward the medical clinic, she says, is to test whether fisetin can reverse decreases in memory once they have already showed up.

Story Source:

The above story is based on materials provided by Salk Institute for Biological Studies.