In a collaboration between the Faculty of Medicine and Surgery of the Catholic University, Rome, and the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, neuroscientists have achieved a significant breakthrough in understanding and manipulating memory-related processes in the brain. This effort, led by Claudio Grassi, Professor of Physiology and Director of the Department of Neuroscience, holds vast potential for advancing our comprehension of memory processes and, crucially, for identifying innovative solutions for neuropsychiatric disorders such as dementia.
The focal point of their research, published in the journal Science Advances, is the LIMK1 protein, a molecule known for its role in memory functions. This protein plays a pivotal role in shaping structural changes in neurons, particularly the formation of dendritic spines, which amplify information transmission within neural networks, playing a critical role in learning and memory.
"Memory is a complex process that involves modifications in synapses, which are the connections between neurons, in specific brain areas such as the hippocampus, which is a neural structure playing a critical role in memory formation," explained Professor Claudio Grassi, senior author of the study. This process is called synaptic plasticity and involves the changes in the structure and function of synapses that occur upon activation of a neural circuit. During this process, complex signaling pathways involving numerous proteins associated with alterations in cognitive functions are activated. One of these proteins is LIMK1. To regulate its activity, researchers integrated a “molecular switch” into the LIMK1 protein, which can be activated by the administration of the drug rapamycin, an immunosuppressive drug known for its beneficial effects on the brain in preclinical models. "Controlling LIMK1 with a drug means being able to promote synaptic plasticity and, therefore, the physiological processes that depend on it," Prof. Grassi elucidates.
First author associate Professor Cristian Ripoli emphasized, "In animals with age-related cognitive decline, using this gene therapy to modify the LIMK1 protein and activate it with the drug resulted in a significant memory improvement. This approach allows us to manipulate synaptic plasticity processes and memory in physiological and pathological conditions. Furthermore, it paves the way for the development of further 'engineered' proteins that could revolutionize research and therapy in the field of neurology.”
"The next step will be to verify the effectiveness of this treatment in experimental models of neurodegenerative diseases exhibiting memory deficits, such as Alzheimer's disease. Further studies will also be necessary to validate the use of this technology in humans," Prof. Grassi concludes, emphasizing the study's transformative implications for the field of neurology.