Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against Trypanosoma cruzi.

Frontiers in Cellular and Infection Microbiology
Gustavo BenaimNathalia Martinez-Sotillo

Abstract

There is no effective cure for Chagas disease, which is caused by infection with the arthropod-borne parasite, Trypanosoma cruzi. In the search for new drugs to treat Chagas disease, potential therapeutic targets have been identified by exploiting the differences between the mechanisms involved in intracellular Ca2+ homeostasis, both in humans and in trypanosomatids. In the trypanosomatid, intracellular Ca2+ regulation requires the concerted action of three intracellular organelles, the endoplasmic reticulum, the single unique mitochondrion, and the acidocalcisomes. The single unique mitochondrion and the acidocalcisomes also play central roles in parasite bioenergetics. At the parasite plasma membrane, a Ca2+--ATPase (PMCA) with significant differences from its human counterpart is responsible for Ca2+ extrusion; a distinctive sphingosine-activated Ca2+ channel controls Ca2+ entrance to the parasite interior. Several potential anti-trypansosomatid drugs have been demonstrated to modulate one or more of these mechanisms for Ca2+ regulation. The antiarrhythmic agent amiodarone and its derivatives have been shown to exert trypanocidal effects through the disruption of parasite Ca2+ homeostasis. Similarly, the amiodarone-derivativ...Continue Reading

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Citations

Nov 28, 2020·Acta Tropica·Isabela Teresa Santos CorreaAndre Gustavo Tempone
Apr 10, 2021·Journal of Experimental Pharmacology·Ana Lia MazzetiVanessa Carla Furtado Mosqueira
Apr 15, 2021·Medicinal Research Reviews·Yash GuptaPrakasha Kempaiah
Apr 16, 2021·Journal of Natural Products·Vinicius S LonderoJoao Henrique G Lago
May 14, 2021·AMB Express·Hamed Memariani, Mojtaba Memariani
Jul 4, 2021·Molecular and Biochemical Parasitology·María C Pérez-GordonesMarta Mendoza
Oct 22, 2021·Frontiers in Cellular and Infection Microbiology·Nubia Carolina Manchola VarónMaria Julia M Alves

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Methods Mentioned

BETA
circular dichroism

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