The genetically modified protein that can enhance memory

The engineered protein is activated by the drug rapamycin, which is known to increase life expectancy in preclinical models.

Scientists have genetically modified a brain molecule called LIMK1 to boost memory. The research team added a “molecular switch” to the protein which can be activated by administering a drug, rapamycin, known for its several anti-ageing effects on the brain.

The immunosuppressive drug is known to increase life expectancy and for its beneficial effects on the brain in preclinical models.

Marrying genetics and chemistry, the authors of the study describe this approach as “chemogenetic”.

Cristian Ripoli, associate professor of physiology at the Catholic University and first author of the study said: “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 expert emphasizes.

Aside from improving scientific understanding of memory function, the research has unlocked potential applications in treating neuropsychiatric diseases like dementia.

The team consisted of neuroscientists from the Faculty of Medicine and Surgery of the Catholic University, Rome and the Fondazione Policlinico Universitario Agostino Gemelli IRCCS.  The study was coordinated by Claudio Grassi, full professor of Physiology and Director of the Department of Neuroscience.

“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,” Grassi said.

“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”

The LIMK1 protein plays a crucial role in determining structural changes in neurons, namely the formation of dendritic spines, which enhance information transmission in neural networks and are crucial in learning and memory processes.

“Some of these proteins are particularly important for memory, in fact, reduced expression or modifications of these proteins are associated with alterations in cognitive functions,” Professor Grassi added.

“One of these proteins is LIMK1. The goal of our study was to regulate the activity of this protein, as it plays a key role in the maturation of dendritic spines between neurons. Controlling LIMK1 with a drug means being able to promote synaptic plasticity and, therefore, the physiological processes that depend on it.”

“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.”

The research was supported by the Italian Ministry of Education, University and Research, the American Alzheimer’s Association Foundation, and the Italian Ministry of Health,