New Memory Research Breakthrough: Genetically Modified LIMK1 Protein Activated With Rapamycin Could Revolutionize Treatment of Memory-Related Neuropsychiatric Diseases and Neuroscience Research.
Researchers from the Faculty of Medicine and Surgery at the Catholic University, Rome and the Fondazione Policlinico Universitario A. Gemelli IRCCS have developed an engineered protein that significantly boosts memory.
Neuroscientists at the Faculty of Medicine and Surgery of the Catholic University, Rome, and the Fondazione Policlinico Universitario Agostino Gemelli IRCCS have genetically modified a molecule, LIMK1, which is crucial for memory function.
They introduced a “molecular switch” that is triggered by administering rapamycin, a drug known for its anti-aging effects on the brain.
Collaborative Study with Significant Implications
This study, published in the journal Science Advances, was a joint effort involving the Catholic University, Rome, and the Fondazione Policlinico Universitario Agostino Gemelli IRCCS. The study was led by Claudio Grassi, Full Professor of Physiology and Director of the Department of Neuroscience.
The research, supported by the Italian Ministry of Education, American Alzheimer’s Association Foundation, and the Italian Ministry of Health, has the potential to enhance our understanding of memory processes and provide new insights into treating neuropsychiatric diseases such as dementia.
The Role of LIMK1 in Memory Processes
The LIMK1 protein is instrumental in shaping structural changes in neurons, particularly the formation of dendritic spines, which play a vital role in information transmission in the brain’s neural networks and are essential for learning and memory.
Prof. Claudio Grassi, senior author of the study, explains: “Memory is a complex process involving modifications in synapses, the connections between neurons, in specific brain areas like the hippocampus, which is crucial for memory formation.
“This phenomenon, known as synaptic plasticity, entails structural and functional changes in synapses that take place when a neural circuit is activated, such as through sensory experiences. These experiences trigger intricate signaling pathways involving numerous proteins,” Prof. Grassi adds.
“Some of these proteins are particularly crucial for memory, and a decrease in their expression or alterations are linked to cognitive function disruptions. LIMK1 is one of these proteins. Our study aimed to regulate the activity of this protein, given its pivotal role in fostering the maturation of dendritic spines between neurons. Exercise control over LIMK1 with a drug means the potential to enhance synaptic plasticity and, consequently, the physiological processes that depend on it,” Prof. Grassi emphasizes.
Chemogenetic Strategy: A New Approach to Memory Enhancement
Cristian Ripoli, Associate Professor of Physiology at the Catholic University and the study’s lead author, adds: “The innovative ‘chemogenetic’ strategy, combining genetics and chemistry, hinges on the use of rapamycin”, an immunosuppressive drug known for extending life expectancy and its beneficial effects on the brain, in preclinical models.”
“We have therefore modified the sequence of the LIMK1 protein by inserting a molecular switch allowing us to trigger it, on demand, through the administration of rapamycin,” Prof. Ripoli emphasizes.
He further notes, “In animals with age-related cognitive decline, implementing this gene therapy to modify the LIMK1 protein and activate it with the drug led to significant memory enhancement. This approach enables the manipulation of synaptic plasticity processes and memory under physiological and pathological conditions. Moreover, it opens the door to developing additional genetically engineered proteins that could revolutionize research and therapy in the field of neurology,” the expert underscores.
Reference: “Engineering memory with an extrinsically disordered kinase” by 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 Saneyoshi, Tommaso Fellin, Yasunori Hayashi and Claudio Grassi, 15 November 2023, Science Advances.
DOI: 10.1126/sciadv.adh1110
