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Metal Ions in Life Sciences Jan 2019Manganese is an essential dietary element that functions primarily as a coenzyme in several biological processes. These processes include, but are not limited to,... (Review)
Review
Manganese is an essential dietary element that functions primarily as a coenzyme in several biological processes. These processes include, but are not limited to, macronutrient metabolism, bone formation, free radical defense systems, and in the brain, ammonia clearance and neurotransmitter synthesis. It is a critical component in dozens of proteins and enzymes, and is found in all tissues. Concentrated levels of Mn are found in tissues rich in mitochondria and melanin, with both, liver, and pancreas having the highest concentrations under normal conditions. However, overexposure to environmental Mn via industrial occupation or contaminated drinking water can lead to toxic brain Mn accumulation that has been associated with neurological impairment. The objective of this chapter is to address the biological importance of Mn (essentiality), routes of exposure, factors dictating Mn status, a brief discussion of Mn neurotoxicity, and proposed methods for neurotoxicity remediation.
Topics: Brain Chemistry; Humans; Manganese
PubMed: 30855111
DOI: 10.1515/9783110527872-016 -
Frontiers in Bioscience (Landmark... Mar 2018Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS),... (Review)
Review
Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.
Topics: Animals; Cation Transport Proteins; Homeostasis; Humans; Ion Transport; Manganese; Manganese Poisoning; Superoxide Dismutase; Tissue Distribution
PubMed: 29293455
DOI: 10.2741/4665 -
Current Environmental Health Reports Sep 2015Exposure to manganese (Mn) causes clinical signs and symptoms resembling, but not identical to, Parkinson's disease. Since our last review on this subject in 2004, the... (Review)
Review
Exposure to manganese (Mn) causes clinical signs and symptoms resembling, but not identical to, Parkinson's disease. Since our last review on this subject in 2004, the past decade has been a thriving period in the history of Mn research. This report provides a comprehensive review on new knowledge gained in the Mn research field. Emerging data suggest that beyond traditionally recognized occupational manganism, Mn exposures and the ensuing toxicities occur in a variety of environmental settings, nutritional sources, contaminated foods, infant formulas, and water, soil, and air with natural or man-made contaminations. Upon fast absorption into the body via oral and inhalation exposures, Mn has a relatively short half-life in blood, yet fairly long half-lives in tissues. Recent data suggest Mn accumulates substantially in bone, with a half-life of about 8-9 years expected in human bones. Mn toxicity has been associated with dopaminergic dysfunction by recent neurochemical analyses and synchrotron X-ray fluorescent imaging studies. Evidence from humans indicates that individual factors such as age, gender, ethnicity, genetics, and pre-existing medical conditions can have profound impacts on Mn toxicities. In addition to body fluid-based biomarkers, new approaches in searching biomarkers of Mn exposure include Mn levels in toenails, non-invasive measurement of Mn in bone, and functional alteration assessments. Comments and recommendations are also provided with regard to the diagnosis of Mn intoxication and clinical intervention. Finally, several hot and promising research areas in the next decade are discussed.
Topics: Absorption, Physiological; Adult; Biomarkers; Environmental Exposure; Female; Half-Life; Humans; Infant; Infant Mortality; Infant, Newborn; Inhalation Exposure; Male; Manganese; Risk Assessment
PubMed: 26231508
DOI: 10.1007/s40572-015-0056-x -
Metallomics : Integrated Biometal... Jun 2016
Topics: Brain; Female; Humans; Lead; Male; Manganese
PubMed: 27261156
DOI: 10.1039/c6mt90017h -
Current Opinion in Chemical Biology Apr 2020Manganese (Mn) plays a complex role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts and is also important for free-living bacteria to thrive in... (Review)
Review
Manganese (Mn) plays a complex role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts and is also important for free-living bacteria to thrive in stressful environments. This review summarizes new aspects of regulatory strategies to control intracellular Mn levels and gives an overview of several newly identified families of bacterial Mn transporters. Recent illustrative examples of advances in quantification of intracellular Mn pools and characterization of the effects of Mn perturbations are highlighted. These discoveries help define mechanisms of Mn selectivity and toxicity and could enable new strategies to combat pathogenic bacteria and promote growth of desirable bacteria.
Topics: Amino Acid Sequence; Bacteria; Bacterial Proteins; Cell Membrane Permeability; Gene Expression Regulation, Bacterial; Homeostasis; Manganese; Membrane Transport Proteins; Mutation; Reactive Oxygen Species; Riboswitch; Substrate Specificity; Superoxide Dismutase; Transcription Factors
PubMed: 32086169
DOI: 10.1016/j.cbpa.2020.01.003 -
Current Environmental Health Reports Dec 2022At elevated levels, the essential element manganese (Mn) is neurotoxic and increasing evidence indicates that environmental Mn exposure early in life negatively affects... (Review)
Review
PURPOSE OF REVIEW
At elevated levels, the essential element manganese (Mn) is neurotoxic and increasing evidence indicates that environmental Mn exposure early in life negatively affects neurodevelopment. In this review, we describe how underlying genetics may confer susceptibility to elevated Mn concentrations and how the epigenetic effects of Mn may explain the association between Mn exposure early in life and its toxic effects later in life.
RECENT FINDINGS
Common polymorphisms in the Mn transporter genes SLC30A10 and SLC39A8 seem to have a large impact on intracellular Mn levels and, in turn, neurotoxicity. Genetic variation in iron regulatory genes may to lesser extent also influence Mn levels and toxicity. Recent studies on Mn and epigenetic mechanisms indicate that Mn-related changes in DNA methylation occur early in life. One human and two animal studies found persistent changes from in utero exposure to Mn but whether these changes have functional effects remains unknown. Genetics seems to play a major role in susceptibility to Mn toxicity and should therefore be considered in risk assessment. Mn appears to interfere with epigenetic processes, potentially leading to persistent changes in developmental programming, which warrants further study.
Topics: Humans; Manganese; Epigenomics; Epigenesis, Genetic
PubMed: 36357556
DOI: 10.1007/s40572-022-00384-2 -
Advances in Nutrition (Bethesda, Md.) May 2017
Topics: Deficiency Diseases; Environmental Exposure; Humans; Manganese
PubMed: 28507016
DOI: 10.3945/an.117.015305 -
International Journal of Molecular... Oct 2023Manganese (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... (Review)
Review
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.
Topics: Humans; Manganese; Diabetes Mellitus, Type 2; Manganese Poisoning; Homeostasis; Neurodegenerative Diseases
PubMed: 37834407
DOI: 10.3390/ijms241914959 -
The Journal of Biological Chemistry May 2020Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes... (Review)
Review
Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.
Topics: Animals; Brain; Cognition; Homeostasis; Humans; Manganese; Neurons; Neurotoxicity Syndromes
PubMed: 32188696
DOI: 10.1074/jbc.REV119.009453 -
Animal Reproduction Science Mar 2022Manganese (Mn) is the twelfth most abundant element in the earth's crust and is widely distributed throughout the surface of the planet, naturally occurring in rocks,... (Review)
Review
Manganese (Mn) is the twelfth most abundant element in the earth's crust and is widely distributed throughout the surface of the planet, naturally occurring in rocks, soil, water, and food. As an essential trace mineral in diets, Mn is required for a variety of metabolic functions including skeletal system development, energy metabolism, enzyme activation, nervous system function, immune system function, and reproductive hormone function. Manganese has effects on reproductive hormone function as a cofactor for enzymes necessary for cholesterol synthesis. Production of steroid hormones necessary for reproduction is dependent on the availability of cholesterol as a precursor. There is also evidence that Mn has effects on reproduction due to actions at the hypothalamus. Because Mn is used for manufacturing of steel, recent research has focused on the effects of Mn toxicity as a result of occupational endeavors rather than evaluating the optimal Mn inclusion rate for mammalian growth and development, reproductive function, immune function, etc. The objective of this review is to address the functions of Mn in reproduction of animals but there is also a focus on other areas of mammalian biology affected by Mn functions, with an emphasis on domestic swine (Sus scrofa).
Topics: Animals; Diet; Hypothalamus; Manganese; Reproduction; Trace Elements
PubMed: 35121412
DOI: 10.1016/j.anireprosci.2022.106924