Role of biometals in pathogenesis treatment of Parkinson's disease (overview)

Abstract

The role of exogenous factors in the occurrence of neurodegenerative diseases has been shown in many works: on the effects of radiation, neurotoxicants, pesticides and other organic and inorganic substances. One of the interesting and promising areas for studying the pathogenesis of neurodegeneration is the analysis of the composition and ratio of trace elements in various tissues and organs of a person. The influence of trace elements on the development of neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease, amyotrophic lateral sclerosis, is given special attention, since such patients show multiple disorders in the homeostasis of the main endogenous brain biometals (calcium, magnesium, zinc, iron, manganese, copper, etc.). On the one hand, in a cell or its components, where metals play a key role in biological processes, a metal deficiency can occur, on the other hand, metals can accumulate in pathological proteins, causing cell dysfunction and death. Protein aggregation is a common feature of all neurodegenerative diseases. Specific changes in the concentration of biometals in various environments of the body can be considered as early biomarkers of neurodegenerations. And the identification of reliable biomarkers is considered a paramount task for the development of the direction of early therapy and prevention of the disease, in particular PD. A change in the distribution of metal, cell deficiency and sequestration in pathological proteins are abnormalities that must be addressed during neurodegeneration. Currently, approximately 800 compounds are used or tested for the treatment of PD, of which approximately 250 have the expected or established chelation properties of metals (CuII, CuI, FeII, FeIII, MnII, ZnII) that are involved in dyshomeostasis in PD. Today's knowledge of the pathogenesis of the most common neurodegenerations, such as AD and PD, is still not enough to develop clear recommendations for therapy with biometals and other trace elements, but work in this direction is actively ongoing.