KANSAS CITY, MO — January 26, 2026 — The mystery of why some memories endure while others fade has intrigued scientists for over a century. Now, groundbreaking research from the Stowers Institute has unveiled a mechanism that transforms fleeting experiences into lasting memories. This study, representing over two decades of work, provides the first direct evidence that the nervous system can intentionally form amyloids to convert sensory experiences into enduring memories. This discovery challenges long-held beliefs about memory and amyloid formation in the brain, opening new avenues for treating amyloid-related neurological disorders.
“I wanted to understand how unstable proteins help create stable memories,” said Dr. Kausik Si, Scientific Director at the Stowers Institute. “We now have definitive evidence that processes within the nervous system can prompt a protein to form an amyloid at a specific time and place, in response to a specific experience.”
Unveiling the Role of Chaperone Proteins
Published in the Proceedings of the National Academy of Sciences on January 30, 2026, the study from the Si Lab focuses on “chaperone proteins” in fruit flies. These proteins guide other proteins to achieve the correct folded state. Traditionally, chaperones were thought to prevent harmful protein misfolding. However, researchers discovered a specific chaperone that allows proteins to change shape, forming functional amyloids crucial for long-term memory.
“This expands the idea of a protein’s capacity to do meaningful things and suggests there is an unknown universe of chaperone biology that we’ve long been missing,” Si explained.
Amyloids: From Disease to Memory
Amyloids are typically linked to neurodegenerative diseases like Alzheimer’s, Huntington’s, and Parkinson’s. These diseases involve amyloids forming tightly packed, stable protein fibers that destroy brain cells and erase memories. However, the new research strengthens the Si Lab’s 2020 study, which proposed that amyloids are not inherently harmful. Instead, they can be controlled and used by the brain to store information, revealing a crucial step in how long-lasting memories are formed.
“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 activate these chaperones to guide toxic amyloids to be less harmful or enhance the brain’s capacity to form functional amyloids.”
Tackling a Century-Old Question
The Si Lab’s 2020 study, led by former Stowers Postdoctoral Research Associate Dr. Rubén Hervas, now a Professor at the University of Hong Kong, revealed that amyloid formation allows animals to form stable memory. “But we did not know how or when,” Si said. The researchers aimed to identify the mechanism controlling this process to manipulate it and influence memory.
“Despite 100 years of studying amyloid biology, nobody has ever asked how the brain can deploy amyloid,” Si explained. “Because amyloid formation was historically thought to be unintentional, it was necessary for us to ask that question.”
A Pivotal Discovery
In 2003, Si discovered a functional amyloid in the sea slug, which has just 10,000 neurons. This was a pivotal step in rethinking amyloid biology. The research expanded to more complex animals, including fruit flies, mice, and humans. The team uncovered that an amyloid-based mechanism is broadly used for memory persistence, with a prion-like protein called Orb2 in fruit flies playing a key role.
The new study allowed the team to test their hypothesis that the difference between harmful and helpful amyloids depends on whether Orb2’s assembly is regulated by other proteins. They identified a previously uncharacterized chaperone, named Funes, inspired by Jorge Luis Borges’ short story “Funes the Memorious,” which affects memory.
Finding Funes: A Key to Memory Formation
The researchers discovered Funes by manipulating the concentrations of 30 different chaperones in the fly’s memory centers. “We trained very hungry fruit flies to link a specific, unpleasant smell with a sugar reward,” said Kyle Patton, Ph.D., lead author of the study. Flies with increased levels of Funes showed a remarkable ability to remember the odor-reward link after 24 hours, a standard proxy for long-term memory.
In Hong Kong, Hervas engineered Funes variants that could bind Orb2 but not trigger its transition into amyloid, resulting in failed long-term memory in flies. This indicated Funes is essential for long-term memory formation.
“We are now getting early evidence that, like the fruit fly shows in this study, the process may also be manifesting in the vertebrate nervous system,” Si said. “Our hypothesis is carrying us all the way to the vertebrate brain, illustrating that it may actually be universal.”
The Implications for Brain Health and Disorders
While screening chaperone proteins in fruit flies, the team discovered an unexpected connection that broadens the study’s relevance. Funes was the most striking chaperone affecting memory, but not the only one. “If you look at the human version of these genes, they have surprisingly been implicated by genome-wide association studies in schizophrenia,” Patton said.
Patton cautioned that this overlap does not mean schizophrenia is a “disease of chaperones,” but it opens the possibility that chaperones could be key factors. “Ultimately, chaperones may allow the brain to perceive, process, or store information about the outside world,” Si said. “In diseases where we do not see the world as it is, like schizophrenia or bipolar disorder, we could imagine chaperones playing a role.”
“While it’s an unknown universe, it’s an exciting one, and we’ll see where we end up,” Si added. “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, an organism that, compared to us, is relatively simple.”
Additional authors of the study include Yangyang Yi, Ph.D., Raj Burt, Kevin K-S. Ng, Ph.D., Mayur Mukhi, and Peerzada Shariq Shaheen Khaki, Ph.D. The research was funded by the Enhanced New Staff Start-up Research Grant from the University of Hong Kong, the Seed Fund for Basic Research from the University of Hong Kong, the Research Grant Council of Hong Kong, and institutional support from the Stowers Institute for Medical Research.
About the Stowers Institute for Medical Research
Founded in 1994 through the generosity of Jim Stowers, founder of American Century Investments, and his wife, Virginia, the Stowers Institute for Medical Research is a non-profit biomedical research organization focused on foundational research. Its mission is to expand our understanding of life’s secrets and improve life’s quality through innovative approaches to the causes, treatment, and prevention of diseases.
The Institute consists of 20 independent research programs and approximately 500 members, over 370 of whom are scientific staff, including principal investigators, technology center directors, postdoctoral scientists, graduate students, and technical support staff. Learn more about the Institute at www.stowers.org and about its graduate program at www.stowers.org/gradschool.
