Signal Transduction: Magnesium Manifests as a Second Messenger

Stangherlin, Alessandra; O’Neill, John S.

doi:10.1016/j.cub.2018.11.003

Cited by 37 publications

(27 citation statements)

References 20 publications

(19 reference statements)

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“…Intracellular Mg 2+ mobilization simultaneously activates CREB and mTOR signaling, and such signaling cooperatively enhances the maturation of neural networks. Notably, the [Mg 2+ ] cyto regulation of mTOR activities exhibits sigmoidal curves, indicating that Mg 2+ functions as a cooperative signal amplifier [38,136]. In the case of the Ca 2+ signal, the conformational changes of a Ca 2+ -binding protein, such as calmodulin, are evolutionarily conserved and play central roles in the switch-like regulation of biochemical reactions.…”

Section: Physiological Roles Of Cellular Mg2+mentioning

confidence: 99%

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

Yamanaka

Shindo

Oka

2019

IJMS

110

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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.

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Section: Physiological Roles Of Cellular Mg2+mentioning

confidence: 99%

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

Yamanaka

Shindo

Oka

2019

IJMS

110

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“…Magnesium is essential to ensure the correct functioning of all human cells, neurons included; it is involved, among others processes, in hundreds of enzymatic reactions [ 28 ], intracellular transmission [ 29 ], myelination process [ 30 ], synapses formation and maintenance [ 31 ] as well as in the regulation of serotoninergic, dopaminergic and cholinergic transmission [ 32 ]. Magnesium is, therefore, an element necessary to maintain neurons healthy and viable [ 33 ], especially because it has been shown to reduce apoptosis in an animal model of induced hypoxia-ischemia [ 34 ] and to prevent synaptic loss in a mouse model of Alzheimer disease [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

The Role and the Effect of Magnesium in Mental Disorders: A Systematic Review

et al. 2020

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Introduction: Magnesium is an essential cation involved in many functions within the central nervous system, including transmission and intracellular signal transduction. Several studies have shown its usefulness in neurological and psychiatric diseases. Furthermore, it seems that magnesium levels are lowered in the course of several mental disorders, especially depression. Objectives: In this study, we wish to evaluate the presence of a relationship between the levels of magnesium and the presence of psychiatric pathology as well as the effectiveness of magnesium as a therapeutic supplementation. Methods: A systematic search of scientific records concerning magnesium in psychiatric disorders published from 2010 up to March 2020 was performed. We collected a total of 32 articles: 18 on Depressive Disorders (DD), four on Anxiety Disorders (AD), four on Attention Deficit Hyperactivity Disorder (ADHD), three on Autism Spectrum Disorder (ASD), one on Obsessive–Compulsive Disorder (OCD), one on Schizophrenia (SCZ) and one on Eating Disorders (ED). Results: Twelve studies highlighted mainly positive results in depressive symptoms. Seven showed a significant correlation between reduced plasma magnesium values and depression measured with psychometric scales. Two papers reported improved depressive symptoms after magnesium intake, two in association with antidepressants, compared to controls. No significant association between magnesium serum levels and panic or Generalized Anxiety Disorder (GAD) patients, in two distinct papers, was found. In two other papers, a reduced Hamilton Anxiety Rating Scale (HAM-A) score in depressed patients correlated with higher levels of magnesium and beneficial levels of magnesium in stressed patients was found. Two papers reported low levels of magnesium in association with ADHD. Only one of three papers showed lower levels of magnesium in ASD. ED and SCZ reported a variation in magnesium levels in some aspects of the disease. Conclusion: The results are not univocal, both in terms of the plasma levels and of therapeutic effects. However, from the available evidence, it emerged that supplementation with magnesium could be beneficial. Therefore, it is necessary to design ad hoc clinical trials to evaluate the efficacy of magnesium alone or together with other drugs (antidepressants) in order to establish the correct use of this cation with potential therapeutic effects.

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“…Besides, Mg 2+ is a central cofactor of many enzymes and regulates especially the activity of glycolytic enzymes in the chelated form of MgATP 2− [74,75,76]. In addition, Mg 2+ is considered to be involved in the intracellular signal transduction as a second messenger [77]. The total intracellular Mg 2+ concentration ([Mg 2+ ] i ) ranges from 17–20 mM, while the free Mg 2+ concentration was estimated to be around 1 mM [69].…”

Section: Genetically Encoded Fluorescent Probes For Alkaline Earthmentioning

confidence: 99%

Live-Cell Imaging of Physiologically Relevant Metal Ions Using Genetically Encoded FRET-Based Probes

Bischof

Burgstaller

Waldeck-Weiermair

et al. 2019

Cells

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Essential biochemical reactions and processes within living organisms are coupled to subcellular fluctuations of metal ions. Disturbances in cellular metal ion homeostasis are frequently associated with pathological alterations, including neurotoxicity causing neurodegeneration, as well as metabolic disorders or cancer. Considering these important aspects of the cellular metal ion homeostasis in health and disease, measurements of subcellular ion signals are of broad scientific interest. The investigation of the cellular ion homeostasis using classical biochemical methods is quite difficult, often even not feasible or requires large cell numbers. Here, we report of genetically encoded fluorescent probes that enable the visualization of metal ion dynamics within individual living cells and their organelles with high temporal and spatial resolution. Generally, these probes consist of specific ion binding domains fused to fluorescent protein(s), altering their fluorescent properties upon ion binding. This review focuses on the functionality and potential of these genetically encoded fluorescent tools which enable monitoring (sub)cellular concentrations of alkali metals such as K+, alkaline earth metals including Mg2+ and Ca2+, and transition metals including Cu+/Cu2+ and Zn2+. Moreover, we discuss possible approaches for the development and application of novel metal ion biosensors for Fe2+/Fe3+, Mn2+ and Na+.

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Signal Transduction: Magnesium Manifests as a Second Messenger

Cited by 37 publications

References 20 publications

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

The Role and the Effect of Magnesium in Mental Disorders: A Systematic Review

Live-Cell Imaging of Physiologically Relevant Metal Ions Using Genetically Encoded FRET-Based Probes

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