Drugs Modulating Calcium Signaling

Dear Colleagues,

Calcium signaling is one of the most important ways of cell communication. It controls a plethora of physiological processes and, therefore, needs to be finely regulated. The alteration of such balance is the chief cause of many diseases. For instance, the only common event observed in the various neurodegenerative diseases is indeed Ca²⁺ overload.

Thus, the “Ca²⁺-antagonists” is one of the classical drug families, which is prescribed for cardiovascular diseases. They reduce the uptake of Ca²⁺ through the voltage-gated Ca²⁺ channels (VGCC), for instance in smooth muscle cells to dissipate hypertension. But despite this essential therapeutic role, cell Ca²⁺ modulators are not usually seen as alternative drugs beyond the cardiovascular system. This is due to the belief that they possess severe adverse effects, such as lowering blood pressure in a patient, which is not a desirable effect unless she/he was hypertensive. By contrast, in the latest decade, a deep knowledge of all types of VGCC and their pharmacological differences, both in the subtype and in the localization, has been documented. This has opened the opportunity to face several neurodegenerative diseases such as Parkinson’s, where a specific VGCC subtype is affected.

On the other hand, cell Ca²⁺ levels are a consequence of the modulated activity of several other Ca²⁺-transporters located not only in the plasma membrane but also in intracellular organelles. These new actors modify the amplitude and the subcellular localization of the Ca²⁺ signal, allowing the generation of “hot spots” in certain subcellular places while avoiding a whole-cell Ca²⁺ overload. To achieve these actions, new drug targets like the Na⁺/Ca²⁺ exchangers (plasmallemal and mitochondrial), the mitochondrial Ca²⁺ uniporter or the newly discovered Ca²⁺ homeostasis modulator 1 channel, can be studied for the discovery of new cell Ca²⁺ modulators. As a consequence, in recent years, medicinal chemists have reported drugs modulating other Ca²⁺ channels, exchangers, or transporters for the treatment of pathologies beyond the cardiovascular ones.

This Special Issue of Molecules titled “Drugs Modulating Ca²⁺ Signaling” is devoted to several research topics related to the search for new chemical entities able to modify the cell Ca²⁺ signal. Topics of interest include (i) computational design, (ii) synthesis, (iii) natural products, (iv) pharmacological screening, (v) structure-activity relationships, (vi) electrophysiology with new Ca²⁺ modulators, (vii) chemical biology, and in general other topics related to the search for new cell Ca²⁺ modulators.

Dr. Cristobal De Los Rios
Guest Editor

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