Hope for Alzheimer's as Neuroscientists Engineer Memory-Boosting Protein

Neuroscientists have engineered a synthetic protein that could boost memory function in individuals with age-associated cognitive decline.

This discovery offers hope to patients with Alzheimer's and other neurodegenerative conditions and promises to "revolutionize" the field of neurology.

"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," Claudio Grassi, a professor of physiology and director of the Department of Neuroscience at the Catholic University, said in a statement.

"This phenomenon, known as synaptic plasticity, involves changes in the structure and function of synapses [the connections between neurons] that occur when a neural circuit is activated, for example, by sensory experiences."

This activation sets off a complex signaling pathway, involving a range of different proteins. "Some of these proteins are particularly important for memory," Grassi said. "In fact reduced expression or modifications of these proteins are associated with alterations in cognitive functions."

One of these molecules is a protein called LIMK1. "The goal of our study was to regulate the activity of this protein, as it plays a key role in the maturation of [connections] between neurons," Grassi said. "Controlling LIMK1 with a drug means being able to promote synaptic plasticity and, therefore, the physiological processes that depend on it."

In a study published in the journal Science Advances on November 15, Grassi and colleagues at the Catholic University and Fondazione Policlinico Universitario Agostino Gemelli, in Rome, Italy, created a genetically modified form of LIMK1 with a "molecular switch" to turn it on and off inside the brain. This molecular switch turns the gene for LIMK1 on in the presence of an immunosuppressive drug called rapamycin, which has been shown to have beneficial effects on the brain.

"The key to this innovative 'chemogenetic' strategy, which combines genetics and chemistry, is precisely linked to the use of rapamycin," Cristian Ripoli, an associate professor of physiology at the Catholic University, and first author of the study, said in a statement. "We have therefore modified the sequence of the LIMK1 protein by inserting a molecular switch that allowed us to activate it, on command, through the administration of rapamycin."

In the study, the team tested the new protein out in animals, with impressive results. "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," Ripoli said. "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."

Further research is required to determine the efficacy of this treatment in humans, but their results offer an exciting future avenue for drug development for diseases such as Alzheimer's.

"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," Grassi said.