◎ Reporter Zhang Jiaxin

Improving memory is an eternal topic of concern for us. As people age, they experience memory loss, which is a natural physiological regularity. At the same time, the most common symptom of some diseases, such as Alzheimer's disease, is memory loss. Is there any way to improve people's memory?

Recently, a paper published in the journal Science Advances said that neuroscientists have designed a synthetic protein that can promote memory function in elderly people with cognitive deterioration. They genetically modified the LIMK1 protein and embedded a synthetic peptide "molecular switch" that can be activated by immunosuppressive drugs to significantly improve memory in experimental animals. This finding holds hope for patients with Alzheimer's disease and other neurodegenerative diseases and is expected to "revolutionize the field of neurology."

Focusing on these questions, the reporter of Science and Technology Daily interviewed Christian Ripoli, the first author of the paper and associate professor of physiology at the Catholic University of the Sacred Heart in Italy, and Claudio Grassi, senior author of the paper, head of the Department of Neuroscience and professor of physiology and psychology at the Catholic University of the Sacred Heart in Italy.

Memorization is a complex process

"Memory is a complex process that involves alterations in synapses located in specific areas of the brain, such as the hippocampus, that connect neurons. This phenomenon of synaptic alteration is called synaptic plasticity. Grassi said.

In an interview, Ripoli told reporters about the process of memory formation: "Memory is often understood as explicit memory. Whereas, explicit memory includes information about places, people, and objects. Clinical evidence and preclinical studies in mammals have identified key brain regions involved in signal processing and memory formation, including the hippocampus and associated areas of the medial temporal lobe. ”

In the neural circuits of these brain regions, synapses transmit information through electrical signals. These transmissions lead to protein modification, activation, or inactivation, and changes in protein expression, which in turn triggers long-term changes in synaptic junction strength. The alterations in these proteins are able to recall the activation of the same neurons at certain moments, helping to preserve and recover memories over time.

So, how do memories increase and weaken? Ripoli says it's about LTP.

Long-term synaptic plasticity refers to the response of neuronal synapses to prolonged stimuli. LTP is an important long-term synaptic plasticity, which means that the synaptic efficiency between neurons can be enhanced for a long time under certain stimulation conditions. Dendritic spines are the main sites for the formation of synapses between neurons. LTP occurs on dendritic spines. On dendritic spines, hundreds of proteins can alter function during LTP occurrence.

Dendritic spines enhance the transmission of information in neural networks and are essential for learning and memory processes. It is through this plasticity that memory is regulated.

LIMK1 is closely related to memory

Unless affected by LTP, dendritic spines maintain a relatively stable structure, Ripoli said. The maintenance of the structure relies on the opposite activity of two proteins (filament and actin). Actin naturally tends to polymerize, whereas filamentin cleaves actin aggregates, creating a kind of equilibrium.

At this point, we have to mention the LIMK1 protein. "The LIMK1 protein is a kinase, a protein that binds adenosine triphosphate (ATP) and phosphorylates its target. "The LIMK1 protein plays a crucial role in determining structural changes in neurons, namely the formation of dendritic spines. ”

The LIMK1 protein phosphorylates filatoin and inhibits it, while allowing actin polymerization and expansion of dendritic spines. By increasing the volume of dendritic spines, neurons communicate more easily.

"In fact, in Alzheimer's disease, the number and volume of dendritic spines decrease. Ripoli said.

This time, the research team aims to modulate the activity of the LIMK1 protein. Controlling the LIMK1 protein with drugs means being able to promote synaptic plasticity, which regulates memory.

The research team designed the LIMK1 protein, in which a synthetic peptide "molecular switch" was introduced, and this "molecular switch" was controlled with rapamycin.

Ripoli said that the LIMK1 protein binds to ATP close to this "molecular switch", and without rapamycin, the synthetic peptide "molecular switch" would remain closed. With rapamycin, the synthetic peptide "molecular switch" is turned on to reactivate the LIMK1 protein.

Ripoli further explained that rapamycin, a drug known for its ability to cross the blood-brain barrier, has been approved by the U.S. Food and Drug Administration (FDA). Studies have shown that it can prolong life and enhance cognitive performance. Therefore, rapamycin may work synergistically with the LIMK1 protein designed by the investigators to potentially slow or reverse cognitive impairment observed in experimental models of various neurological and psychiatric disorders.

Whether it can be used in humans needs to be further verified

"The engineered LIMK1 protein enhances memory in mice by increasing dendritic spine volume and neural communication in the hippocampus," Ripoli said. This improvement was significant for older mice with cognitive deficits, who showed signs of improved memory in tests such as recognition of new objects and recognition of the location of objects. ”

This approach enables researchers to manipulate synaptic plasticity processes and memory under physiological and pathological conditions. In addition, Grassi stressed that it paves the way for the development of further engineered proteins that could revolutionize research and treatment in the field of neurology.

Next, Grassi said, they will verify the effectiveness of this treatment in experimental models of neurodegenerative diseases that exhibit memory deficits, such as Alzheimer's disease. Of course, more research is needed to confirm whether this method can be safely and effectively applied to humans.