Scientists at the Faculty of Medicine and Surgery of Catholic University, Rome, and the Fondazione Policlinico Universitario Agostino Gemelli IRCCS have genetically modified a molecule, the protein LIMK1, which is normally active in the brain, with a key role in memory. They added a “molecular switch” that is activated by administering a drug, rapamycin, known for its several anti-aging effects on the brain.

Their findings are published in Science Advances in an article titled, “Engineering memory with an extrinsically disordered kinase.”

“Synaptic plasticity plays a crucial role in memory formation by regulating the communication between neurons,” the researchers wrote. “Although actin polymerization has been linked to synaptic plasticity and dendritic spine stability, the causal link between actin polymerization and memory encoding has not been identified yet…Using an extrinsically disordered form of the protein kinase LIMK1, which rapidly and precisely acts on ADF/cofilin, a direct modifier of actin, we induced long-term enlargement of dendritic spines and enhancement of synaptic transmission in the hippocampus on command.”

Claudio Grassi, senior author of the study, explained: “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. This phenomenon, known as synaptic plasticity, involves changes in the structure and function of synapses that occur when a neural circuit is activated, for example, by sensory experiences. These experiences promote the activation of complex signaling pathways involving numerous proteins.

Cristian Ripoli, associate professor of physiology at Catholic University, and first author of the study, added: “The key to this innovative ‘chemogenetic’ strategy, which combines genetics and chemistry, is precisely linked to the use of rapamycin,” an immunosuppressive drug known to increase life expectancy and for its beneficial effects on the brain, in preclinical models.

This approach allowed the scientists to manipulate synaptic plasticity processes and memory in physiological and pathological conditions. Their findings may pave the way for the development of further “engineered” proteins that could revolutionize research and therapy in the field of neurology.

Looking toward the future, the scientists will verify the effectiveness of their treatment in experimental models of neurodegenerative diseases such as Alzheimer’s disease. Further studies will also be needed to validate the use of the technology in humans.

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