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Review
, 20 (14)

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

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Review

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

Ryu Yamanaka et al. Int J Mol Sci.

Abstract

Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, the homeostasis of intracellular Mg2+ is physiologically linked to growth, proliferation, differentiation, energy metabolism, and death of cells. On the cellular and tissue levels, maintaining Mg2+ within optimal levels according to the biological context, such as cell types, developmental stages, extracellular environments, and pathophysiological conditions, is crucial for development, normal functions, and diseases. Hence, Mg2+ is pathologically involved in cancers, diabetes, and neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and demyelination. In the research field regarding the roles and mechanisms of Mg2+ regulation, numerous controversies caused by its versatility and complexity still exist. As Mg2+, at least, plays critical roles in neuronal development, healthy normal functions, and diseases, appropriate Mg2+ supplementation exhibits neurotrophic effects in a majority of cases. Hence, the control of Mg2+ homeostasis can be a candidate for therapeutic targets in neuronal diseases. In this review, recent results regarding the roles of intracellular Mg2+ and its regulatory system in determining the cell phenotype, fate, and diseases in the nervous system are summarized, and an overview of the comprehensive roles of Mg2+ is provided.

Keywords: differentiation; intracellular signal; magnesium; neural network maturation; neurodegenerative disease; neuron; synaptogenesis.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Magnesium homeostasis in whole body and brain. (A) Magnesium metabolism of the human body. (B) Choroid plexus and blood–brain barrier in the human brain. (C) The enlarged image of the boxed region in panel B, i.e., choroid plexus. The enlarged image of the boxed region in the panel B, i.e., blood–brain barrier (BBB). The gradient of [Mg2+] between blood and cerebrospinal fluid (CSF). (D) The structure of BBB at cellular levels and the comparison of [Mg2+] between blood, extracellular fluid (ECF) and CSF.
Figure 2
Figure 2
Intracellular Mg2+ distribution and machinery for Mg2+ regulation: The intracellular Mg2+ content is regulated by the balance of influx, efflux, and the intracellularly stored amount. Major storages for intracellular Mg2+ are the nuclei, mitochondria, ERs, and the ribosome. Cytosolic Mg2+ is bound to phosphometabolites, such as ATP. NIPA1, NIPA2, NIPA3, NIPA4, MagT1, TRPM6, TRPM7 and SLC41A2 contributes the uptake of extracellular Mg2+. Na+/Mg2+ and H+/Mg2+ exchangers contribute the Mg2+ efflux. Some studies support that SLC41A1, CNNM2 and CNNM4 functions as Mg2+ exchangers. MMgT1/2 and HIP14/14L is localized at golgi apparatus, and Mrs2 and SLC41A3 is localized at mitochondria. Abbreviations: ER—endoplasmic reticulum; ATP—adenosine 5’-triphosphate; TRPM6—transient receptor potential melastatin 6; TRPM7—transient receptor potential melastatin 7; CNNM2 or ACDP2—cyclin M2; CNNM4—cyclin M4.
Figure 3
Figure 3
Overview of cell physiology of Mg2+. The intracellular Mg2+ plays versatile roles in neurons. Abbreviations: PI3K—phosphatidylinositol-3 kinase; mTOR—mechanistic target of rapamycin; JNK—c-Jun NH2-terminal kinase; ERK—extracellular signal-regulated kinase; CREB—cAMP response element binding; ROS—reactive oxygen species; NMDA—N-methyl-D-aspartate; AD—Alzheimer’s disease; PD—Parkinson’s disease; ATP—adenosine 5’-triphosphate; PTP—permeability transition pore; RyR—ryanodine receptor; IP3R—inositol-1,4,5-trisphosphate receptor; OXPHOS—oxidative phosphorylation; mtDNA—mitochondrial DNA.

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References

    1. Romani A.M.P. Cellular magnesium homeostasis. Arch. Biochem. Biophys. 2011;512:1–23. doi: 10.1016/j.abb.2011.05.010. - DOI - PMC - PubMed
    1. Wolf F.I., Trapani V. Cell (patho)physiology of magnesium. Clin. Sci. (Lond.) 2008;114:27–35. doi: 10.1042/CS20070129. - DOI - PubMed
    1. De Baaij J.H.F., Hoenderop J.G.J., Bindels R.J.M. Magnesium in man: implications for health and disease. Physiol. Rev. 2015;95:1–46. doi: 10.1152/physrev.00012.2014. - DOI - PubMed
    1. Anastassopoulou J., Theophanides T. Magnesium-DNA interactions and the possible relation of magnesium to carcinogenesis. Irradiation and free radicals. Crit. Rev. Oncol. Hematol. 2002;42:79–91. doi: 10.1016/S1040-8428(02)00006-9. - DOI - PubMed
    1. Holm N.G. The significance of Mg in prebiotic geochemistry. Geobiology. 2012;10:269–279. doi: 10.1111/j.1472-4669.2012.00323.x. - DOI - PMC - PubMed
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