Why do some memories linger for decades while others vanish overnight? A team at the Stowers Institute for Medical Research believes they’ve found the answer, and it lies in a surprising place: proteins that deliberately form amyloids.
The study, set to publish in the Proceedings of the National Academy of Sciences on January 30, provides the first direct evidence that the nervous system can harness amyloids, structures long associated with devastating brain diseases, to preserve experiences.
“I wanted to understand how unstable proteins help create stable memories,” said Kausik Si, Ph.D., Scientific Director at Stowers. “And now, we have definitive evidence that there are processes within the nervous system that can take a protein and make it form an amyloid at a very specific time, in a specific place, and in response to a specific experience.”
Amyloids are usually cast as villains. In Alzheimer’s, Huntington’s, and Parkinson’s disease, they form dense clumps that choke neurons and erase memory. But Si’s lab has spent two decades showing that not all amyloids are destructive. Some, when carefully regulated, act as scaffolds that stabilize memory.
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The new research identifies a chaperone protein in fruit flies that guides this process. Chaperones typically help proteins fold correctly or prevent harmful clumping. Here, however, scientists found one that does the opposite: it allows proteins to reshape into functional amyloids that lock memories in place.
The team named the protein Funes, after Jorge Luis Borges’ short story Funes the Memorious, about a man cursed with perfect recall.
“We trained very hungry fruit flies to link a specific, unpleasant smell with a sugar reward,” explained lead author Kyle Patton, Ph.D. Flies with higher levels of Funes remembered the odor-reward link a full day later, a standard marker of long-term memory.
At the molecular level, experiments showed that without Funes, the flies failed to form lasting memories. “The fact that amyloid is needed to form memory implied there must be a mechanism that controls the process,” said co-author Rubén Hervas, Ph.D., now at the University of Hong Kong.
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Si first discovered functional amyloids in sea slugs in 2003. Since then, his lab has traced the phenomenon across species, from fruit flies to mice to humans. The new findings suggest the mechanism may be universal.
Intriguingly, human versions of the chaperone genes have been linked in genetic studies to schizophrenia. Patton cautioned that this doesn’t mean schizophrenia is “a disease of chaperones,” but the overlap hints that these proteins could influence how the brain perceives reality.
The discovery could reshape how scientists think about memory and how they approach amyloid-related diseases.
“Discovering this chaperone protein has now provided us with an avenue to potentially approach amyloid-based diseases in an unanticipated way,” Si said. “It may be possible to either activate these chaperones and guide toxic amyloids to be less harmful, or, by activating them, we can potentially endow the brain with enhanced capacity to form functional amyloids.”
For now, the work remains in fruit flies. But the implications stretch far beyond the lab. If amyloids can be deliberately controlled, therapies might one day transform how we treat memory loss, psychiatric disorders, or even enhance memory itself.
“While it’s an unknown universe, it’s an exciting one,” Si said. “What’s remarkable is that we’re now thinking about new ways to treat human diseases, and it all started by studying the sea slug.”
