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Drugs Modulating Calcium Signaling

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 4945

Special Issue Editor


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Guest Editor
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, 28006 Madrid, Spain
Interests: design and synthesis of innovative drugs; phosphatase enzymes up-regulators; modulation of the cell calcium signal; purinergic receptors antagonists
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Special Issue Information

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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Keywords

  • Calcium
  • Cell Ca2+ signal
  • Ca2+ channels and transporters
  • Neurodegenerative diseases
  • Cardiovascular diseases
  • Second messenger

Published Papers (1 paper)

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Research

10 pages, 2317 KiB  
Article
Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells
by Chang-Hyun Park, Ji Hoon Song, Su-Nam Kim, Ji Hwan Lee, Hae-Jeung Lee, Ki Sung Kang and Hyung-Ho Lim
Molecules 2020, 25(1), 144; https://doi.org/10.3390/molecules25010144 - 30 Dec 2019
Cited by 26 | Viewed by 4541
Abstract
In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted [...] Read more.
In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases. Full article
(This article belongs to the Special Issue Drugs Modulating Calcium Signaling)
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