A study of St Petersburg University chemists will help to better understand the mechanisms of neurodegenerative diseases

The results of the project "Metalloproteins and Low-molecular Forms of Selenium, Copper and Manganese in the Etiology of Neurodegenerative Diseases", supported by an RFFR grant, are published in the journals Analytica Chimica Acta, the Journal of Trace Elements in Medicine and Biology, and Neurodegenerative Diseases and Biological Trace Element Research.

The nerve cells of people who suffer from neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, etc.) gradually die. Dementia, impaired movement and other pathologies of the nervous system can also be provoked by a high concentration of metals in the body. American epidemiologists from South Dakota first studied the toxicity of selenium and its influence on the development of muscular dystrophy. In this state there is a geological anomaly - an increased content of selenium in the soil, which leads to massive muscular dystrophy in cattle. A similar situation was observed in the Italian region of Emilia-Romagna. High concentration levels of selenium in local tap water have caused an increased number of cases of amyotrophic lateral sclerosis (ALS) among local residents.

"Selenium is like a rock star with a bad reputation. Scientists are still arguing about the benefits and harms of this trace element. Some believe that the amount of selenium in the body should be increased, because it is responsible for antioxidant protection. In addition, the unique mechanism of how selenium realises its vital functions is significantly different from other trace elements; it occurs directly on the ribosome during protein synthesis, which attracts to it increasing research interest. Another group of specialists refers to studies according to which excess selenium contributes to the development of cancer and second type diabetes. I think the truth is somewhere in the middle: according to EU recommendations, selenium should enter the body in quantities of about 80 micrograms per day, ", says Associate Professor of St Petersburg University Nikolay Solovyov, who is leading the research team.

Metals contained in the body participate in the metabolism, and therefore are always toxic in high concentrations. For example, manganese and copper are able to induce oxidative cascades, which poison the body. At the same time, these same metals are included in the composition of enzymes that slow these cascades. Thus, the same elements simultaneously destroy the body and protect it from negative impacts.

The St Petersburg University scientists made a contribution to the study of this phenomenon. In collaboration with Italian colleagues, they are conducting a study on the effect of certain metals on the development of ALS. The chemists are developing techniques for determining the chemical forms of metals to study their biological activity, in particular, their transportation and metabolism in the central nervous system.

"The vital trace elements as selenium, copper and manganese, bind to specific carrier proteins in order to penetrate in a controlled and dosed way through physiological barriers primarily to the brain. These complexes with proteins - high molecular weight chemical forms - are biologically active and have a strictly defined function, for example, enzymatic or signal. On the other hand, with excessive intake of micro-elements or a breakdown in their metabolism, the concentration of metals, not associated with proteins, i.e. low molecular weight chemical forms increases in the body. These forms are generally responsible for toxicity and other undesirable effects. We are interested in studying the behaviour of metals in the central nervous system, and therefore we are working with samples of cerebrospinal fluid, the biological environment of the organism, which is directly in contact with the brain tissue," said Associate Professor Nikolay Solovyov, St Petersburg University. Analysis of cerebrospinal fluid is one of the few ways to find out what is happening chemically in the human brain. As an additional object of research, the project also studies the chemical forms of selenium, copper and manganese in the blood serum.

"We determine the concentration of chemical forms of metals in the cerebrospinal fluid using mass spectrometry (a supersensitive analytical method) and chromatography. The very process of research is rather complicated, since metals in this liquid are in small quantities: for example, selenium is only about two micrograms in one litre. This creates difficulties not only at the stage of developing the methodology, but also in interpreting the results and controlling the quality of measurements. Another problem is that traditional methods of sample preparation, adopted in elemental analysis, are, as a rule, inapplicable," said Nikolay Solovyov.

According to the expert, it is not easy to get research samples. The fact is that sampling of cerebrospinal fluid is produced with the help of a special needle. There is a risk that the patient will remain paralysed below the waist after this procedure. To avoid unjustified risks, cerebrospinal fluid can be obtained for analysis only according to the prescriptions of a neurologist and only for the clinical diagnosis of certain diseases. The remainder of the bio-sample can be used for scientific purposes.

The St Petersburg University study will help epidemiologists, biologists and physicians to determine pathological processes occurring in patients suffering from neurodegenerative diseases. In addition, the data obtained will make it possible to establish concentration levels at which selenium, copper and manganese are safe for the human body.