Researchers at the Catholic University of Rome’s Faculty of Medicine and Surgery and the A. Gemelli National Polyclinic Foundation IRCCS have developed an artificial protein that improves memory.
Neuroscientists at the Faculty of Medicine and Surgery of the Catholic University of Rome and the Agostino Gemelli National Polikuri Foundation IRCCS genetically modified a molecule called LIMK1, a protein that normally operates in the brain and plays an important role in memory.
They added a “molecular switch” activated by administering rapamycin, a drug known for some anti-aging effects on the brain.
Collaborative research with important implications
This is the research result published in the journal scientific progressIt involves the Catholic University of Rome and the Agostino Gemelli National Polyclinic Foundation IRCCS. The study was coordinated by Claudio Grassi, full professor of physiology and chair of the neuroscience department.
This research was supported by the Italian Ministry of Education, Universities and Research and the U.S. government. Alzheimer’s disease The Association Foundation and the Italian Ministry of Health have great application potential by deepening our understanding of memory function and facilitating the identification of innovative solutions for neuropsychiatric diseases such as dementia.
Role of LIMK1 in memory processes
The LIMK1 protein plays an important role in determining structural changes in neurons, namely the formation of dendritic spines. Dendritic spines enhance information transmission in neural networks and are important for learning and memory processes.
Professor Claudio Grassi, senior author of the study, explains: “Memory is a complex process that involves changes in synapses, connections between neurons, in specific brain regions such as the hippocampus, a neural structure that plays an important role in memory formation.”
“This phenomenon, known as synaptic plasticity, involves changes in the structure and function of synapses that occur when neural circuits are activated, such as by sensory experiences. It promotes the activation of signal transduction pathways,” Professor Grassi added.
“Some of these proteins are particularly important for memory, and in fact, decreased expression or modification of these proteins is associated with changes in cognitive function. One of these proteins is LIMK1. The goal of our study was to control the activity of this protein, as it plays an important role in the maturation of dendritic spines. We have shown that controlling LIMK1 with drugs can promote synaptic plasticity. meaning that it can promote the physiological processes that depend on it,” Professor Grassi emphasizes.
Chemogenetic strategies: a new approach to memory enhancement
“The key to this innovative ‘chemogenetics’ strategy, which combines genetics and chemistry, is the use of the immunosuppressive drug rapamycin,” said Christian Ripoli, associate professor of physiology at Catholic University and lead author of the study. It is precisely connected to this,” he added. The drug is known to increase life expectancy and have beneficial effects on the brain in preclinical models. ”
“We therefore modified the sequence of the LIMK1 protein by inserting a molecular switch that can activate it on command through the administration of rapamycin,” emphasizes Professor Lipoli.
“Using this gene therapy to modify the LIMK1 protein and activate it with a drug significantly improved memory in animals with age-related cognitive decline. This makes it possible to manipulate synaptic plasticity processes and memory in clinical conditions, and paves the way for the development of further “engineered” proteins that could revolutionize research and treatment in the field of neurology. ”, experts emphasize.
“The next step is to test the effectiveness of this treatment in experimental models of neurodegenerative diseases that exhibit memory impairment, such as Alzheimer’s disease. Further research is also needed to validate the use of this technology in humans. “Professor Grassi concluded.
Reference: “Manipulation of memory by exogenous disordered kinases” Cristian Ripoli, Onur Dagliyan, Pietro Renna, Francesco Pastore, Fabiola Paciello, Raimondo Sollazzo, Marco Rinaudo, Martina Battistoni, Sara Martini, Antonella Tramutola, Andrea Sattin, Eugenio Barone, Takeo Written by Saneyoshi, Tommaso Ferrin, Yasunori Hayashi, Claudio Grassi, November 15, 2023, scientific progress.