麻豆淫院

Tiny gold particles that act as carriers for lithium can be delivered directly to the brain in the form of a nasal spray. Developed by scientists at the Universit脿 Cattolica Rome campus/Fondazione Policlinico Universitario A. Gemelli IRCCS, the new nanotechnological device can be used for the treatment and prevention of neuropsychiatric and neurodegenerative diseases.

Lithium is already in clinical use for manic-depressive syndrome, but in oral formulation it is not free of side effects. It is used to combat neuropsychiatric diseases such as bipolar disorder, neurodegenerative diseases such as Alzheimer's disease, and brain infections such as those caused by Herpes Simplex Virus type 1, which several recent studies have linked to an increased risk of neurological diseases.

in the journal Advanced Materials and already patented, the idea is the result of a study that demonstrated that it is possible to directly inhibit the activity of an enzyme that plays a key role in the development of these diseases (glycogen synthase kinase-3 beta, GSK-3尾) directly in the brain by using lithium delivered by intranasally administered gold nanoparticles.

The research team was led by Roberto Piacentini, associate professor of physiology at Universit脿 Cattolica/Fondazione Policlinico Universitario A. Gemelli IRCCS; Antonio Buonerba, associate professor of inorganic chemistry at the University of Salerno; Alfonso Grassi, full professor of inorganic chemistry at the University of Salerno; and Claudio Grassi, professor of physiology and director of the Department of Neuroscience at the Universit脿 Cattolica/Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

This innovative therapeutic approach achieves the same effects as orally administered lithium but using significantly lower concentrations of this ion and targeting it specifically to the brain, thereby reducing the risk of side effects.

In the study, the researchers demonstrated the effectiveness of this new nanotechnological device in inhibiting the activity of the GSK-3尾 enzyme in the hippocampus and restoring memory already compromised in an experimental model of Alzheimer's disease, without adverse events in the treated animals.

Studies are currently underway to verify other areas of application for this device and to complete its safety assessment in order to proceed quickly with its clinical application.

GSK-3尾, lithium and gold nanoparticles

GSK-3尾 is an enzyme that is essential for many cellular functions: It is estimated that more than 100 proteins are targeted by this kinase, which is a molecular machine that attaches a chemical group (phosphate) to other molecules, so modifying their function. Abnormal activation of this enzyme can therefore cause malfunctioning of the target proteins and promote the onset of various diseases.

In the case of neurodegenerative diseases, such as Alzheimer's disease, or neuropsychiatric disorders such as bipolar disorder, hyperactivation of the GSK-3尾 enzyme is observed, which in turn involves key proteins, such as tau protein, and aberrant activation of the Wnt/尾-catenin pathway, involved in the entry of various viruses, such as Herpes Simplex 1 and SARS-CoV-2. Controlling the activation of this enzyme in specific areas of the brain could thus counteract the onset of these diseases.

Lithium is a potent inhibitor of GSK-3尾. The concentrations of lithium needed to counteract the molecular mechanisms responsible for neurodegenerative diseases or viral infections affecting the central nervous system are higher than those considered acceptable in terms of risk/benefit ratio, significantly limiting the therapeutic applications of the drug.

Professor Piacentini explains, "Our challenge was to develop a device that would allow us to exploit the therapeutic potential of lithium without causing adverse effects and that could be delivered in a site-specific manner, avoiding systemic administration."

Professor Buonerba adds, "Gold nanoparticles are the optimal tool for this type of strategy. They can be functionalized with glutathione, which, on the one hand, promotes the formation of aggregates that easily enter cells and, on the other, allows molecules or ions, such as lithium, to bind. Once the nanoparticle aggregates enter the cells, they are broken down and the lithium is released into the cells, allowing effective therapeutic concentrations of this ion to be obtained with low doses of administration."

Professor Piacentini continues, "Furthermore, the intranasal route is an elective route for directly targeting the brain and bypassing the systemic circulation, thus optimizing the safety of our nanodevice. Gold, an inert metal that has already been proven to be harmless in biological systems, is eliminated through renal excretion, limiting its accumulation in the brain following repeated administrations over time."

Professor Antonio Buonerba states, "The versatility of this new pharmaceutical vector is extraordinary. The nanoparticles developed can be loaded with different pharmacological active ingredients and are able to evade biological cellular defenses, allowing their targeted transport to specific physiological active sites."

"In this work we have shown that 5 days of administration of gold nanoparticles functionalized with glutathione and coated with lithium (called LiG-AuNPs) can significantly inhibit the activity of GSK-3尾 kinase in the hippocampus of mice, and that the same treatment repeated for two months leads to a significant regression of the memory deficit exhibited by a mouse model of Alzheimer's disease, analyzed at the behavioral and molecular levels," first author Dr. Giulia Puliatti explains.

Toward new treatment possibilities

Professor Claudio Grassi emphasizes, "To date, lithium-based drugs are widely used for the treatment of neuropsychiatric diseases, but unfortunately, they are not without significant side effects. Taken orally in tablet form, lithium reaches the brain through the bloodstream and therefore ends up exerting toxic effects on other organs such as the kidneys and thyroid.

"Achieving effective concentrations of lithium in nerve cells through 'brain-targeted' administration of low doses of the ion with the aid of gold nanoparticles is therefore an important innovation for the development of new and safer ways of treating patients.

"We believe that our nanotechnological tool can enable the development of new therapeutic approaches not only for psychiatric disorders but also for neurodegenerative and viral diseases in which altered GSK-3尾 activity in the brain plays a key role."

Professor Alfonso Grassi concludes, "Finally, our nanoparticles can be synthesized very easily and that simplifies the production process, keeping low the costs of manufacturing a product that may be launched on the pharmaceutical market in the near future."