Abstract
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.
Highlights
Mn is the 12th most abundant element and 5th most abundant metal on the earth
Given its paramangnetic property, Mn serves as a contrast agent in medical magnetic resonance imaging (MRI) [2, 3].In the infant food industry, Mn is commonly added to total parenteral nutrition (TPN) at significant concentrations as an essential nutrient [4]
In both industrial workers exposed to high levels of Mn and individuals carrying genomic mutations without high environmental Mn exposure, MRI studies showed that in the brain, Mn preferentially accumulates in the globus pallidus, followed by putamen, caudate, midbrain, cerebellum, subthalamic and dentate nucleus and sparing of the thalamus and ventral pons [8, 48, 59, 71]
Summary
Mn is the 12th most abundant element and 5th most abundant metal on the earth. This metal has a silver-grey color and is very easy to oxidize. The primary target tissue of Mn toxicity is the brain, and “manganism” refers to a variety of psychiatric and motor disturbances caused by excessive Mn accumulation. Irritability, mood changes and compulsive behaviors are first noticed in the patients [6]; later on, the symptoms get more prominent with four-limb dystonia, an upright stance, tremors at rest and a signature high-stepping gait [7, 8]. These symptoms resemble, are not identical to symptoms of idiopathic Parkinson’s disease (PD) [9]. Mn overexposure can impair cardiovascular function, causing abnormal electrocardiogram, increased heartbeat, shorter P-R interval and lower diastolic blood pressure [11]
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