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http://mfa.gov.il/mfa/innovativeisr...ein-manipulation-aids-memory-12-may-2015.aspx
Researchers find a way to improve memory by suppressing a protein molecule that links aging to Alzheimer’s disease.
Prof. Kobi Rosenblum
Copyright: Gil Nehushtan/University of Haifa
By Avigayil Kadesh
Scientists from Israel report they have found a way to improve memory by manipulating PERK, a specific protein molecule known to function poorly in old age. PERK is known to be closely linked to Alzheimer’s disease.
"We know that in Alzheimer’s, PERK doesn't function properly,” said Prof. Kobi Rosenblum, who heads the University of Haifa lab in which the research was done. “Our success in manipulating its expression without causing any harm to the proper functioning of the brain paves the way for improving memory and perhaps even slowing the pathological development of diseases like Alzheimer’s.”
Rosenblum’s lab at the university’s Sagol Department of Neurobiology researches brain and cognitive function in normal and disease states, in an effort to discover new ways to fight brain diseases that affect behavior and personality.
Previous studies here and in other labs throughout the world had shown that the brain’s process of formulating memory is linked to the synthesis of proteins. High rates of protein production will lead to a strong long-term memory, while a slow rate of protein production leads to weak memories likely to be forgotten.
In the current study, Rosenblum lab members Hadile Ounallah-Saad and Vijendra Sharma examined the activity of elF2 alpha, a protein that’s known as the “spigot,” or regulator, that determines the pace of protein synthesis in the brain during memory formation.
They already knew three main molecules affect the action of protein, so their first task was to determine the relative importance of each of these molecules in controlling the activity of efF2 alpha -- and as a result, the ability to create and store memories. Tests at the tissue and cell levels led the researchers to discover that the main molecule controlling the efF2 alpha’s activity is PERK.
"The fact that we identified PERK as the primary controller had particular significance,” said Ounallah-Saad. “Firstly, of course, we identified the dominant component. Secondly, from previous studies we already knew that in degenerative diseases like Alzheimer’s, PERK performs deficiently. Third, PERK acts on various cells, including neurons, as a monitor and controller of metabolic stress.
“In other words, we found a molecule that has a major impact on the process of creating and formulating memory, and which we know performs deficiently in people with Alzheimer’s disease.”
Improved memory and cognitive abilities
During the second stage of the study, the researchers tried to improve the memory of lab rats by manipulating this molecule.
They used two accepted methods: one is a drug called a small-molecule inhibitor; the other involves making a genetic change to the brain cells via a type of virus commonly used in gene therapy.
After suppressing PERK’s activity by applying gene therapy -- with the help of Efrat Edry from the university’s Center for Gene Manipulation in the Brain -- the researchers measured a 30 percent increase in the rats’ memory of either positive or negative experiences.
The rodents also demonstrated improved long-term memory and enhanced behavioral plasticity, meaning they were better able to “forget” a bad experience.
When the researchers examined the tissues on a cell and molecular level, they were able to confirm that the steps they’d taken had indeed stopped the expression of PERK, which allowed the “spigot” – the elF2 alpha protein – to perform better and to pick up the pace of protein synthesis.
There was a clear correlation between memory function and the degree to which PERK was suppressed, too. The more efficiently PERK was suppressed, the better the memory function.
“The brain operates in a most sophisticated fashion, with each action closely linked to many other actions,” said Ounallah-Saad. “In our study we succeeded in maintaining control of the PERK such that it didn't influence the retrieval of existing memories, or do any other cognitive damage.”
Rosenblum explained that the study has proven it is possible to strengthen the process of protein synthesis in the brain and create stronger memories that last a long time.
“The moment we did this by manipulating a molecule that we know performs deficiently in people with Alzheimer’s and is linked to the aging process, we paved the way for the possible development of drugs that can slow the progress of incurable diseases like degenerative brain conditions, Alzheimer’s chief among them,” said Rosenblum.
The results of the Israeli study were published recently in the Journal of Neuroscience.