RUDN University Doctors Study the Harm to the Brain Induced by Manganese
Manganese regulates the development of the nervous system, helps to control the metabolism within the cell, redox reactions, urea transformations. Usually, a person receives enough manganese with food, so a deficiency of this element is rare. At the same time, an overexposure can cause serious poisoning—the brain function is disrupted and the risk of neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, increases. RUDN University doctors have summarized the data that will help save people from manganese poisoning.
"Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. Мы изучили работы, связанные с исследованиями нейротоксичности марганца за последние пять лет", said Aksana Mazilina, Ph.D., associate professor at the Department of Medical Elementology of RUDN University.
Over the past five years, the majority of the studies was devoted to the role of the proteins SLC39A14, SLC39A8 and SLC30A10, which supply manganese inside the cell. Excess manganese harms the nervous system due to the connection of this element with large proteins SNARE and NLRP3. This causes inflammation of the nervous tissue and disrupts the work of synapses—structures of nerve cells that releases neurotransmitters. Manganese also affects the accumulation of alpha-synuclein, a protein that is considered a marker of Parkinson's disease. In addition, there is a possibility that manganese can affect the production of proteins of certain genes and damage these mechanisms epigenetically.
By analyzing the genome and the entire set of metabolic processes, scientists have discovered the mechanisms of metabolism that are disrupted due to the toxic effect of manganese. Among them are the regulation of oxidative stress, apoptosis and other mechanisms of "cellular suicide", neuroinflammation, as well as disruption of the work of energy producers in the cell (mitochondria) and neurotransmitters.
Scientists constantly find new mechanisms manganese overexposure affects the nervous system. However, the experimental evidence base is still small—studies are conducted mainly in vitro, and not on living organisms. Therefore, the doctors of the RUDN University suggested that it is possible to determine the most harmful of them in experimental studies in vivo.
Although recent findings demonstrated the potential targets for Mn neurotoxicity, in vitro experiments were carried out much more often than in vivo. certain in vivo studies also used animal models exposed to physiologically and environmentally irrelevant Mn doses. Therefore, despite multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity and testify to their relevance to human diseases", said Aksana Mazilina, Ph.D., associate professor at the Department of Medical Elementology of RUDN University
Alexey A. Tinkov et al, Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update, International Journal of Molecular Sciences (2021). DOI: 10.3390/ijms22094646
Provided by RUDN University