24 November 2022

Partial protection

Neuroscientists of St. Petersburg State University, universities of Belgium and Italy have found a new way to partially restore memory in Alzheimer's disease

An international group of scientists, which included the director of the Institute of Translational Biomedicine of St. Petersburg State University Raul Gainetdinov, has discovered an innovative approach to the treatment of cognitive impairment in Alzheimer's disease. Neuroscientists have found that activation of the TAAR1 receptor can partially improve memory and prevent the development of psychoses in patients. The findings of scientists will help in the development of new drugs for the disease.

Alzheimer's disease is a neurodegenerative disorder that affects at least 27 million people on the planet. Patients with this diagnosis have disorders of short-term and long-term memory, problems with speech, perception and orientation in space, loss of motor functions and psychosis. It is believed that beta-amyloid peptide (Aß peptide) is involved in the development of Alzheimer's disease. With excessive accumulation in the body, it begins to form amyloid plaques — structures of improperly folded proteins that do not dissolve, are not excreted and eventually cause the death of brain neurons.

Most significantly, beta-amyloid peptide impairs the work of the glutamate neurotransmitter system, which is responsible for the cognitive functions of the body, primarily for memorization and learning. Deposition of the Aß peptide leads to the fact that part of the glutamate receptors moves from the cell surface inside, due to which the transmission of signals between neurons and cells is disrupted, and cognitive processes malfunction.

Scientists from St. Petersburg State University, the Italian Institute of Technology, the University of Milan and For the first time, the University of Mons has found an approach to the treatment of Alzheimer's disease that will prevent it.

The researchers found that the work of the glutamate system can be influenced by the trace-amine receptor TAAR1.

Trace amines, or trace amines, are cousins of dopamine and serotonin. Receptors for these substances were discovered relatively recently, about 20 years ago. There are six subtypes of such receptors in humans, and TAAR1 is the most studied of them.

Early studies have shown that TAAR1 is involved in the regulation of a person's emotional state, and therefore, by acting on this receptor, it is possible to relieve patients from various mental disorders. In particular, activation of TAAR1 has been proven to treat schizophrenia.

In their new study, neuroscientists from St. Petersburg State University, universities in Belgium and Italy tested whether it is possible to achieve improvements in Alzheimer's disease in a similar way. To do this, scientists using the Aß peptide reproduced at the cellular level failures in the glutamate system, and then added the TAAR1 activator to the test tubes with samples.

"Thanks to this, glutamate receptors, which were "hiding" inside the cells due to the accumulation of beta-amyloid peptide, moved back to the surface and became active. As a result, the function of the glutamate system has largely recovered. We found a similar effect when working with mice," said St. Petersburg State University Professor Raul Gainetdinov.

As part of the study, scientists studied the condition of animals in which, due to the high concentration of the peptide in the body And then there were symptoms similar to Alzheimer's disease, namely dementia and psychosis. Neuroscientists injected TAAR1 activator into one group of mice, the second group did not receive such therapy.

As a result, animals with an activated receptor behaved much more calmly. They also partially recovered their memory, thanks to which the mice from this group coped more effectively with the test for passing the Y-maze — they remembered better and more often which of the corridors they needed to turn to find food.

"Based on the results obtained, it can be assumed that drugs acting on TAAR1 can become a "double blow" to Alzheimer's disease — they will simultaneously restore cognitive functions and additionally cause an antipsychotic effect," Raul Gainetdinov emphasizes.

The professor noted that a new generation of drugs regulating the activity of the TAAR1 receptor and aimed at the treatment of schizophrenia are already being prepared for market entry in the USA and Switzerland. They will be the first antipsychotic drugs in the world that do not block dopamine receptors, due to which they have minimal side effects. The findings of a new work by neuroscientists from St. Petersburg State University, Belgium and Italy will help start clinical trials of these drugs for subsequent use in Alzheimer's disease.

Article by Leo et al. Trace Amine Associate Receptor 1 (TAAR1) as a New Target for the Treatment of Cognitive Dysfunction in Alzheimer's Disease is published in the International Journal of Molecular Sciences.

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