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.
Highlights
Magnesium (Mg) is the second-most abundant cation following potassium in mammalian cells, and it is essential for numerous cellular processes, including enzymatic reactions, ion channel functions, metabolic cycles, and cellular signaling, as well as the stability of biomolecules, such as RNA, DNA, and proteins [1,2,3]
In MPP+-induced mitochondrial stress in the Parkinson’s disease (PD) model, the cytosolic Mg2+ level after mobilization from the mitochondria and extracellular medium is correlated with the cell viability [39]
As the NMDA receptor is involved in excitatory neurotransmission, neuroplasticity, and neuroexcitotoxicity, it plays an important role in developmental plasticity [146,147], learning and memory [32], and circadian clock rhythm [148]
Summary
Magnesium (Mg) is the second-most abundant cation following potassium in mammalian cells, and it is essential for numerous cellular processes, including enzymatic reactions, ion channel functions, metabolic cycles, and cellular signaling, as well as the stability of biomolecules, such as RNA, DNA, and proteins [1,2,3]. Because of the essential roles of Mg2+, fundamental requirements of Mg2+ for biological processes seem to pose constraints on the evolution of cells and organisms. This fundamental nature of Mg2+ in life leads to the versatility and universality of the roles of Mg2+ in living systems. The homeostasis of intracellular Mg2+ is physiologically linked to cell growth, differentiation, energy metabolism, and cell death via the control of enzymatic activities, channel openings, DNA/RNA stability, and cellular stress [1,2,3]. The significance of intracellular Mg2+ is universal and fundamental at the molecular level, but its multiple and complex functions lead to its cell-type-specific roles. The aim is to summarize the findings regarding the roles of intracellular Mg2+ and its regulatory system for determining cell phenotypes and fates in the nervous system and to provide an overview of the comprehensive roles of Mg2+ in neuro(patho)physiology
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