Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders

Manganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to a...

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Main Authors: Giuseppe Magro, Vincenzo Laterza, Federico Tosto, Angelo Torrente
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Journal of Xenobiotics
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Online Access:https://www.mdpi.com/2039-4713/15/2/54
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author Giuseppe Magro
Vincenzo Laterza
Federico Tosto
Angelo Torrente
author_facet Giuseppe Magro
Vincenzo Laterza
Federico Tosto
Angelo Torrente
author_sort Giuseppe Magro
collection DOAJ
description Manganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to as manganism, which shares some similarities with Parkinson’s disease. Mn levels seem regulated by many transporters responsible for its uptake and efflux. These transporters play an established role in many inherited disorders of Mn metabolism and neurotoxicity. Some inherited Mn metabolism disorders, caused by mutations of SLC30A10 and SLC39A14, assume crucial importance since earlier treatment results in a better prognosis. Physicians should be familiar with the clinical presentation of these disorders as the underlying cause of dystonia/parkinsonism and look for other accompanying features, such as liver disease and polycythemia, which are typically associated with SLC30A10 mutations. This review aims to highlight the currently known Mn transporters, Mn-related neurotoxicity, and its consequences, and it provides an overview of inherited and acquired disorders of Mn metabolism. Currently available treatments are also discussed, focusing on the most frequently encountered presentations.
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spelling doaj-art-97aa895c41de4bcbbc4b68ef6ed8a0f62025-08-20T02:18:19ZengMDPI AGJournal of Xenobiotics2039-47052039-47132025-04-011525410.3390/jox15020054Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired DisordersGiuseppe Magro0Vincenzo Laterza1Federico Tosto2Angelo Torrente3Department of Neuroscience, “Giovanni Paolo II” Hospital, Lamezia Terme, 88100 Catanzaro, ItalyDepartment of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, 88100 Catanzaro, ItalyDepartment of Neuroscience, “Giovanni Paolo II” Hospital, Lamezia Terme, 88100 Catanzaro, ItalyDepartment of Biomedicine, Neuroscience, and Advanced Diagnostics (BiND), University of Palermo, 90129 Palermo, ItalyManganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to as manganism, which shares some similarities with Parkinson’s disease. Mn levels seem regulated by many transporters responsible for its uptake and efflux. These transporters play an established role in many inherited disorders of Mn metabolism and neurotoxicity. Some inherited Mn metabolism disorders, caused by mutations of SLC30A10 and SLC39A14, assume crucial importance since earlier treatment results in a better prognosis. Physicians should be familiar with the clinical presentation of these disorders as the underlying cause of dystonia/parkinsonism and look for other accompanying features, such as liver disease and polycythemia, which are typically associated with SLC30A10 mutations. This review aims to highlight the currently known Mn transporters, Mn-related neurotoxicity, and its consequences, and it provides an overview of inherited and acquired disorders of Mn metabolism. Currently available treatments are also discussed, focusing on the most frequently encountered presentations.https://www.mdpi.com/2039-4713/15/2/54manganesehypomanganesemiahypermanganesemiamanganese neurotoxicitymanganese exposed workersmanganism
spellingShingle Giuseppe Magro
Vincenzo Laterza
Federico Tosto
Angelo Torrente
Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders
Journal of Xenobiotics
manganese
hypomanganesemia
hypermanganesemia
manganese neurotoxicity
manganese exposed workers
manganism
title Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders
title_full Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders
title_fullStr Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders
title_full_unstemmed Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders
title_short Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders
title_sort manganese neurotoxicity a comprehensive review of pathophysiology and inherited and acquired disorders
topic manganese
hypomanganesemia
hypermanganesemia
manganese neurotoxicity
manganese exposed workers
manganism
url https://www.mdpi.com/2039-4713/15/2/54
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AT federicotosto manganeseneurotoxicityacomprehensivereviewofpathophysiologyandinheritedandacquireddisorders
AT angelotorrente manganeseneurotoxicityacomprehensivereviewofpathophysiologyandinheritedandacquireddisorders