Here\u2019s what you\u2019ll learn when you read this story:<\/p>\n
Amyloid proteins are typically considered bad guys, playing front-and-center roles in diseases such as Alzheimer\u2019s and Parkinson\u2019s.<\/p>\n
However, for nearly two decades, the Stowers Institute in Kansas City has been investigating whether a functional version of amyloids may be key to forming long-term memories from sensory experiences.<\/p>\n
In a new study, scientists at the institute unlocked another key part of the memory-forming process by identifying a type of chaperone protein in the brain of a fruit fly that helps amyloids form memories\u2014and that could unlock novel therapies for neurological diseases.<\/p>\n
The story of your life is encoded in your memories<\/a>, but scientists don\u2019t have a strong grasp on exactly how the brain turns a fleeting sensory experience into a lasting recollection. And it turns out that one of the key drivers of neurological diseases, including those associated with losing your memory, might be responsible for creating long-term memories in the first place.<\/p>\n In a new study published in the journal Proceedings of the National Academy of Sciences<\/a> (PNAS), neuroscientist Kausik Si and his team at the Stowers Institute in Kansas City, Missouri, analyzed \u201cchaperone proteins\u201d\u2014proteins that help fold other proteins into correct states\u2014in the brains of fruit flies<\/a>. Despite being the size of a grain of sand, a fruit fly brains contains over 150 yards of neural wiring that binds 140,000 neurons into a web called the connectome. In 2024, scientists<\/a> successfully mapped the fruit fly connectome, and it now often serves as a model for exploring the inner workings of the biological mind.<\/p>\n Si and his team found that one kind of chaperone protein allows for the creation of functional amyloids\u2014clumps of protein whose folded-up shapes makes them useful inside the brain. In their pathological form, amyloids are often associated with Alzheimer\u2019s and Parkinson\u2019s diseases, as they typically form tightly packed and (unfortunately) detrimental protein fibers that destroy brain cells<\/a> and, in turn, memories. However, when it comes to making memories, functional amyloids appear to play a surprisingly central role.<\/p>\n \u201cWe have definitive evidence that there are processes within the nervous system<\/a> 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,\u201d Si said in a press statement<\/a>.<\/p>\n Si is no stranger to exploring the potential positive, memory-producing effects of amyloids. Back in 2003, he discovered functional amyloids in sea slugs, and in a 2020 study published in the journal Science<\/a>, Si\u2019s lab reported that amyloids functioned as adaptive proteins for the formation of memories. At the time of the latter study, according to Si, his team \u201cdid not know how or when\u201d amyloids<\/a> could play a positive role in memory formation, but \u201cthe fact that amyloid is needed to form memory implied there must be a mechanism that controls the process.\u201d<\/p>\n In their current study, Si\u2019s team went about resolving this mystery by manipulating the concentrations of 30 different chaperone proteins<\/a> in the fly\u2019s memory center. In the process, the scientists uncovered a previously undescribed chaperone protein they nicknamed \u201cFunes,\u201d after the main character in Jorge Luis Borges\u2019 short story \u201cFunes the Memorious,\u201d who gains the ability to remember absolutely everything in perfect detail.<\/p>\n To test their hypothesis that Funes chaperone proteins were responsible for creating the amyloids behind memory formation, the scientists trained fruit flies to expect a sugary reward after being exposed to an unpleasant smell<\/a>. Flies with increased levels of Funes successfully remembered the reward linked with the odor after 24 hours. Additional research at the University of Hong Kong studied engineered variants of the Funes chaperone protein that bound to Orb2 (called CPEB in mammals)\u2014a kind of protein that\u2019s involved in memory formation in fruit flies. Unlike the original Funes chaperone proteins, these variants did not trigger the formation of amyloids. But remarkably, the flies with these variant chaperones failed to form long-term memories, demonstrating that amyloid folding is critical to long-term memory formation.<\/p>\n