Researchers from the Faculty of Medicine and Surgery of the Catholic University, Rome, and the Fondazione Policlinico Universitario Agostino Gemelli IRCCS have made a groundbreaking breakthrough by genetically modifying a molecule that plays a vital role in the brain memory function.
Mechanisms in Memory Formation
Memory is a complex process involving synapse modifications or the connections between neurons. These modifications occur in specific brain areas, such as the hippocampus, a neural structure that plays a critical role in forming memories.
Memory formation also involves a phenomenon known as synaptic plasticity, where changes in the structure and function of synapses happen as sensory experiences activate the neural circuit. Such experiences promote the activation of complex signaling pathways that involve numerous proteins.
Some of these proteins are crucial for memory. In fact, reducing the expression or modifications of such proteins can alter cognitive functions. One of these proteins is LIMK1, which plays a significant role in determining the structural changes in neurons. It is involved in forming dendritic spines, which enhance information transmission in neural networks and are essential in learning and memory processes.
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Engineered Protein Enhancement
The ability of dendritic spines to change their structure is believed to be involved in the long-term potentiation of glutamatergic synapses, which is assumed to be important in creating long-term memories. Actin polymerization also plays an important role in the structural plasticity of dendritic spines by allowing their cytoskeletons to be remodeled.
In this study entitled "Engineering memory with an extrinsically disordered kinase," the researchers aim to regulate the activity of LIMK1, focusing on its key role in the maturation of dendritic spines between neurons. Controlling LIMK1 with a drug means promoting synaptic plasticity and the physiological processes that depend on it.
The key to this innovative 'chemogenetic' technique, which combines genetics and chemistry, is linked to using rapamycin. This substance is an immunosuppressive drug known for having beneficial effects on the brain in preclinical models and increasing life expectancy.
Led by Catholic University associate professor Cristian Ripoli, the research team modified the sequence of the LIMK1 protein by inserting a molecular switch. This technique enabled the experts to activate the protein on command by administering rapamycin.
The researchers tested this gene therapy in modifying the LIMK1 protein of animals with age-related cognitive decline. A significant memory was shown upon activation of the drug. This approach allowed the researchers to manipulate synaptic plasticity processes and memory in physiological and pathological conditions.
This research also has great potential in improving our understanding of memory functions and in facilitating the identification of innovative solutions for neuropsychiatric disorders such as dementia. It can also pave the way for developing further 'engineered' proteins, which could revolutionize research and therapy in the field of neurology.
In the future, the research team aims to test the effectiveness of this treatment in experimental models of neurodegenerative diseases that inhibit memory deficits, like Alzheimer's disease. Further steps will be necessary to validate the potential use of this technology in humans.
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