Improving cognition and identifying abnormal molecular pathways in Alzheimer’s disease has been challenging. Current studies of Alzheimer’s disease have focused on reducing such occurrences as amyloid plaque, neuroinflammation, and neurofibrillary tangles.
In this regard, SciTech News and the Science Signaling journal recently published reports on findings from the Signaling study. Results of the study suggest that normal brain activity which is necessary for memory formation but is lost through Alzheimer’s disease may be revived through synthetic pharmaceuticals.
About Protein Synthesis
Protein synthesis balances the loss of cellular proteins destroyed during the production of new proteins.
The lead author of the study, Dr. M. Martins-Oliveira of the Center for Neural Science at NYU, explained that the Signaling study, the first of its kind, found that a pharmacological approach to the reversal of defective protein synthesis in Alzheimer’s disease was effective in mice.
The process that has been identified by the study addresses the loss of cognitive functions such as thinking, learning, and memory consolidation. The synthesis (combination) of new proteins is necessary for neuronal function in the brain and memory consolidation.
Dr. Martins-Oliveira stated that the medical community had previously recognized signs of impaired protein synthesis in mice.
Neuroscientists had also shown evidence that memory deficits occur in mouse models due to impaired protein synthesis in the brain. The next logical step was to consider the rescue of brain protein synthesis and potential improvement in memory function in Alzheimer’s disease.
Professor Eric Klann, the senior co-author of the study at NYU’s Neural Science Center, confirmed that activating the brain’s protein synthesis may restore lost cognitive functions.
About the Signaling Study
The Signaling study focused on ISRIB, which is a synthetic molecule that boosts protein synthesis. ISRIB targets genetic code translation resulting in protein production.
The researchers then addressed the issue of whether ISRIB could restore the brain’s ability to change and then to learn (synaptic plasticity) as well as restore memory.
In previous studies, it had been shown that translation initiation is defective in the brains of Alzheimer’s patients. This brought the researchers to the next step, which was that ISRIB may be able to restore areas of cognitive functions.
First, the team established that critical aspects of the protein synthesis mechanism are at low levels in the brain structure (hippocampus) of Alzheimer’s patients. The hippocampus is significantly involved with memory. Therefore, the researchers suspected that protein synthesis would also be disrupted.
Navigating the Maze
The next step involved testing mice who had conditions similar to Alzheimer’s disease to determine if ISRIB was able to restore their memory. It was at this point that the team discovered that ISRIB could not only restore protein synthesis in the hippocampus, but it may also restore memory functions.
The researchers concluded that based on their findings the restoration of protein synthesis with the addition of synthetic molecules such as ISRIB may revive cognitive processes that are disrupted by Alzheimer’s disease.