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

IF 4.4 Q1 TOXICOLOGY

Journal of Xenobiotics Pub Date : 2025-04-04 DOI:10.3390/jox15020054

Giuseppe Magro, Vincenzo Laterza, Federico Tosto, Angelo Torrente

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Abstract

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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锰神经毒性：病理生理学和遗传及获得性疾病的综合综述。

锰（Mn）是人体必需的微量元素，也是线粒体超氧化物歧化酶等几种关键酶的辅助因子。因此，它对活性氧起着重要的防御作用。尽管如此，锰长期过度暴露会导致一种被称为锰中毒的神经系统疾病，这与帕金森病有一些相似之处。锰水平似乎受许多负责其摄取和外排的转运蛋白的调节。这些转运蛋白在许多Mn代谢和神经毒性的遗传性疾病中发挥着既定的作用。一些由SLC30A10和SLC39A14突变引起的遗传性锰代谢紊乱具有至关重要的意义，因为早期治疗可导致更好的预后。医生应该熟悉这些疾病的临床表现，作为肌张力障碍/帕金森病的潜在原因，并寻找其他伴随特征，如肝脏疾病和红细胞增多症，这些通常与SLC30A10突变相关。本文综述了目前已知的锰转运蛋白、锰相关的神经毒性及其后果，并概述了锰代谢的遗传和获得性疾病。目前可用的治疗方法也进行了讨论，重点是最常见的表现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Xenobiotics TOXICOLOGY-

CiteScore

5.30

自引率

1.70%

发文量

审稿时长

10 weeks

期刊介绍： The Journal of Xenobiotics publishes original studies concerning the beneficial (pharmacology) and detrimental effects (toxicology) of xenobiotics in all organisms. A xenobiotic (“stranger to life”) is defined as a chemical that is not usually found at significant concentrations or expected to reside for long periods in organisms. In addition to man-made chemicals, natural products could also be of interest if they have potent biological properties, special medicinal properties or that a given organism is at risk of exposure in the environment. Topics dealing with abiotic- and biotic-based transformations in various media (xenobiochemistry) and environmental toxicology are also of interest. Areas of interests include the identification of key physical and chemical properties of molecules that predict biological effects and persistence in the environment; the molecular mode of action of xenobiotics; biochemical and physiological interactions leading to change in organism health; pathophysiological interactions of natural and synthetic chemicals; development of biochemical indicators including new “-omics” approaches to identify biomarkers of exposure or effects for xenobiotics.