Abstract
This review focuses on the current knowledge on the involvement of metal ions in signaling processes within the cell, in both physiological and pathological conditions. The first section is devoted to the recent discoveries on magnesium and calcium-dependent signal transduction—the most recognized signaling agents among metals. The following sections then describe signaling pathways where zinc, copper, and iron play a key role. There are many systems in which changes in intra- and extra-cellular zinc and copper concentrations have been linked to important downstream events, especially in nervous signal transduction. Iron signaling is mostly related with its homeostasis. However, it is also involved in a recently discovered type of programmed cell death, ferroptosis. The important differences in metal ion signaling, and its disease-leading alterations, are also discussed.
Highlights
Signal transduction and spreading is a key cellular process in maintaining life and its development
Many controversies still exist regarding the roles of magnesium in cell signaling
Magnesium has a crucial role in numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, and DNA/RNA stabilities
Summary
Signal transduction and spreading is a key cellular process in maintaining life and its development. Changes in the concentration of metal ions affect the signaling processes in both excitable and non-excitable cells on both sides of the cellular membrane [3,4,5,6]. Recent studies indicate that metal ions, such as zinc and copper, may be released to the synaptic cleft [7,8,9] This phenomenon is still not fully understood; it is a very interesting example of signaling involving metal ions. Many new studies and conclusions have appeared in this field recently and will be discussed in this review Studies show that both the normal aging of the brain and the development of diseases, such as neurodegenerative and psychiatric disorders, are manifested by deregulation of the management of metal ions such as iron, zinc, and copper. While the pathological role of metal ions is still under investigation, it may arise from homeostasis disorders, which, in turn, may be related to disorders of metal ions sensing by different cells
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