"Since the development of a basic understanding of the biochemical pathways involved in memory formation, the holy grail of CNS research in the pharmaceutical industry is the identification of a safe, orally active drug that activates memory-associated pathways and enhances memory," says lead author Pamela Maher, Ph.D., a researcher in the Cellular Neurobiology Laboratory at the Salk Institute.
Maher hit upon the beneficial effects of fisetin when she
screened a collection of flavonoids, substances with anti-oxidant activities found in many plants, for their neuroprotective abilities in tissue culture models of neurodegenerative disease.
found that some of those compounds, including fisetin, induced differentiation or maturation of neural cells.
explains, "That suggested to us that these compounds might be particularly beneficial, since they might not only protect neural cells from dying but might be able to promote new connections between nerve cells."
Interestingly the signaling pathway activated by fisetin in neural differentiation also played a role in memory formation, a process neuroscientists call "long-term potentiation" or LTP.
LTP allows memories to be stored in the brain by strengthening connections between neurons.
"We wanted to find out whether we could detect any effects of fisetin on long-term potentiation and the formation of memories in animals," Maher recalls.
Since the hippocampus plays an important role in establishing new memories, Maher, and co-authors Tatsuhiro Akaishi and Kazuho Abe, both at Musashino University in Tokyo, Japan, extended the study and found that fisetin activates the same signaling pathway in rat hippocampal tissues and also induces LTP.
"The good news is that fisetin is readily available in strawberries but the bad news is that because of its natural product status there may be little financial interest in getting it into human clinical trials for diseases associated with memory loss such as Alzheimer's, where the treatment options are currently very limited," says Maher