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Review
. 2017 Jun;4(2):223-228.
doi: 10.1007/s40572-017-0136-1.

Relationships Between Essential Manganese Biology and Manganese Toxicity in Neurological Disease

Anna C Pfalzer  1   2 , Aaron B Bowman  3   4   5
Affiliations
Review

Relationships Between Essential Manganese Biology and Manganese Toxicity in Neurological Disease

Anna C Pfalzer et al. Curr Environ Health Rep. 2017 Jun.

Abstract

Purpose of review: Manganese (Mn) is critical for neurodevelopment but also has been implicated in the pathophysiology of several neurological diseases. We discuss how Mn requirements intersect with Mn biology and toxicity, and how these requirements may be altered in neurological disease. Furthermore, we discuss the emerging evidence that the level of Mn associated with optimal overall efficiency for Mn biology does not necessarily coincide with optimal cognitive outcomes.

Recent findings: Studies have linked Mn exposures with urea cycle metabolism and autophagy, with evidence that exposures typically neurotoxic may be able to correct deficiencies in these processes at least short term. The line between Mn-dependent biology and toxicity is thus blurred. Further, new work suggests that Mn exposures correlating to optimal cognitive scores in children are associated with cognitive decline in adults. This review explores relationships between Mn-dependent neurobiology and Mn-dependent neurotoxicity. We propose the hypothesis that Mn levels/exposures that are toxic to some biological processes are beneficial for other biological processes and influenced by developmental stage and disease state.

Keywords: Aging; Mn biology; Neurological disease; Neurotoxicity.

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Figures

Figure 1
Figure 1
Discrepancies between efficacy of Mn-dependent biology and Mn toxicity in the context of neurological disease and age. Discrepancies between A) select Mn-dependent enzymes, B) the efficacy of Mn biology and optimal neurodevelopment and cognition, and C) the efficacy of Mn biology and Mn toxicity. The gray double-sided arrow in (C) indicates that the degree of overlap between optimal Mn biology and Mn toxicity may change with age or disease state. Superoxide dismutase (SOD); Arginase (ARG); Glutamine synthetase (GS), the relationship between efficacy and Mn exposure in vivo is not clear, thus individual curves are arbitrary.
See this image and copyright information in PMC

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