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Review
. 2023 Oct 6;24(19):14959.
doi: 10.3390/ijms241914959.

Consequences of Disturbing Manganese Homeostasis

Jacek Baj  1 , Wojciech Flieger  1 , Aleksandra Barbachowska  2 , Beata Kowalska  3 , Michał Flieger  4 , Alicja Forma  1 , Grzegorz Teresiński  4 , Piero Portincasa  5 , Grzegorz Buszewicz  4 , Elżbieta Radzikowska-Büchner  6 , Jolanta Flieger  7
Affiliations
Review

Consequences of Disturbing Manganese Homeostasis

Jacek Baj et al. Int J Mol Sci. .

Abstract

Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved in energy metabolism, the endogenous antioxidant enzyme systems, neurotransmitter production, and the regulation of reproductive hormones. However, overexposure to Mn is toxic, particularly to the central nervous system (CNS) due to it causing the progressive destruction of nerve cells. Exposure to manganese is widespread and occurs by inhalation, ingestion, or dermal contact. Associations have been observed between Mn accumulation and neurodegenerative diseases such as manganism, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. People with genetic diseases associated with a mutation in the gene associated with impaired Mn excretion, kidney disease, iron deficiency, or a vegetarian diet are at particular risk of excessive exposure to Mn. This review has collected data on the current knowledge of the source of Mn exposure, the experimental data supporting the dispersive accumulation of Mn in the brain, the controversies surrounding the reference values of biomarkers related to Mn status in different matrices, and the competitiveness of Mn with other metals, such as iron (Fe), magnesium (Mg), zinc (Zn), copper (Cu), lead (Pb), calcium (Ca). The disturbed homeostasis of Mn in the body has been connected with susceptibility to neurodegenerative diseases, fertility, and infectious diseases. The current evidence on the involvement of Mn in metabolic diseases, such as type 2 diabetes mellitus/insulin resistance, osteoporosis, obesity, atherosclerosis, and non-alcoholic fatty liver disease, was collected and discussed.

Keywords: exposure to manganese; manganese; manganese neurotoxicity; manganese toxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Main exposure routes and physiological functions of Mn in humans.
Figure 2
Figure 2
Effects of Mn dysregulation.
Figure 3
Figure 3
The U-shaped curve for risk associated with Mn status in the body.
Figure 4
Figure 4
A model of the imbalance in the Mn transport system.
Figure 5
Figure 5
Hypermagnesemia−dystonia KEGG pathway (map:hsa04216) that corresponds to ferroptosis. Fe-Transferrin transport is shown in purple. The transport proteins ZIP8 and ZIP14, which support the transcellular transport of divalent Mn ions within the microvascular capillary endothelial cells (BMVECs) and the blood–brain barrier (BBB), are marked in red (network H01938 Hypermanganesemia with dystonia). (generated online from https://www.genome.jp/entry/H01938) (accessed on 6 March 2023).
See this image and copyright information in PMC

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