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

摘要: There is no effective cure for Chagas disease, which caused by infection with the arthropod-borne parasite, Trypanosoma cruzi. In search new drugs to treat potential therapeutic targets have been identified exploiting differences between mechanisms involved in intracellular Ca2+ homeostasis, both humans and trypanosomatids. trypanosomatid, regulation requires concerted action of three organelles, endoplasmic reticulum, single unique mitochondrion, acidocalcisomes. The mitochondrion acidocalcisomes also play central roles parasite bioenergetics. At plasma membrane, a Ca2+--ATPase (PMCA) significant from its human counterpart responsible extrusion; distinctive sphingosine-activated channel controls entrance interior. Several anti-trypansosomatid demonstrated modulate one or more these regulation. antiarrhythmic agent amiodarone derivatives shown exert trypanocidal effects through disruption homeostasis. Similarly, amiodarone-derivative dronedarone disrupts homeostasis T. cruzi epimastigotes, collapsing mitochondrial membrane (ΔΨm), inducing large increase concentration ([Ca2+]i) this organelle cytoplasm. same general mechanism has SQ109, anti-tuberculosis drug potent effect. Miltefosine similarly induces [Ca2+]i acting on channel, These examples, conjunction other evidence we review herein, strongly support targeting as strategy against disease.