The effects of manganese overexposure on brain health

Miah, Mahfuzur R.; Ijomone, Omamuyovwi M.; Okoh, Comfort O A; Ijomone, Olayemi K.; Akingbade, Grace T.; Ke, Tao; Krum, Bárbara Nunes; Martins, Airton da Cunha; Akinyemi, Ayodele Jacob; Aranoff, Nicole; Soares, Félix Alexandre Antunes; Bowman, Aaron B.; Aschner, Michael

doi:10.1016/j.neuint.2020.104688

Cited by 88 publications

(36 citation statements)

References 145 publications

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“…However, the case for dietary Mn deficiency appears to be extremely rare in humans due to high levels of Mn in dietary products [7,8]. In contrast, Mn overexposure, which is far more common, may cause brain-associated disorders [9]. Studies on neurological outcomes have been carried out in populations living in areas near industrial activities, including former and active Mn alloys plants, and Mn ore processing plants [10][11][12][13], among others.…”

Section: Introductionmentioning

confidence: 99%

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Tinkov

Paoliello

Mazilina

et al. 2021

IJMS

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Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

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Section: Introductionmentioning

confidence: 99%

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Tinkov

Paoliello

Mazilina

et al. 2021

IJMS

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“…However, the rise of manganese utility in the industry has led to increased manganese pollution. The imbalance of manganese homeostasis has the potential to cause neurodegenerative diseases ( 33 , 34 ). Specially, epidemiological investigations indicate that excessive exposure to manganese increases the risk of PD ( 34 , 35 , 36 ).…”

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confidence: 99%

“…The imbalance of manganese homeostasis has the potential to cause neurodegenerative diseases ( 33 , 34 ). Specially, epidemiological investigations indicate that excessive exposure to manganese increases the risk of PD ( 34 , 35 , 36 ). Multiple studies demonstrated that occupational manganese exposure during welding, mining, and other related industrial activities is associated with Parkinsonism ( 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ).…”

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confidence: 99%

Manganese promotes α-synuclein amyloid aggregation through the induction of protein phase transition

Huang

Liu

et al. 2022

Journal of Biological Chemistry

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“…They all cause neurotoxic effects [ 3 ]. Manganese (Mn) is another neurotoxic element of growing concern in terms of environmental overexposures [ 4 ]. Sources of human environmental exposure are diverse, from air, food, or drinking water.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Environmental Metal Neurotoxicity: A Focus on the Interactions of Metals with Synapse Structure and Function

Carmona

Roudeau

Ortega

2021

Toxics

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Environmental exposure to neurotoxic metals and metalloids such as arsenic, cadmium, lead, mercury, or manganese is a global health concern affecting millions of people worldwide. Depending on the period of exposure over a lifetime, environmental metals can alter neurodevelopment, neurobehavior, and cognition and cause neurodegeneration. There is increasing evidence linking environmental exposure to metal contaminants to the etiology of neurological diseases in early life (e.g., autism spectrum disorder) or late life (e.g., Alzheimer’s disease). The known main molecular mechanisms of metal-induced toxicity in cells are the generation of reactive oxygen species, the interaction with sulfhydryl chemical groups in proteins (e.g., cysteine), and the competition of toxic metals with binding sites of essential metals (e.g., Fe, Cu, Zn). In neurons, these molecular interactions can alter the functions of neurotransmitter receptors, the cytoskeleton and scaffolding synaptic proteins, thereby disrupting synaptic structure and function. Loss of synaptic connectivity may precede more drastic alterations such as neurodegeneration. In this article, we will review the molecular mechanisms of metal-induced synaptic neurotoxicity.

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The effects of manganese overexposure on brain health

Cited by 88 publications

References 145 publications

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Manganese promotes α-synuclein amyloid aggregation through the induction of protein phase transition

Molecular Mechanisms of Environmental Metal Neurotoxicity: A Focus on the Interactions of Metals with Synapse Structure and Function

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