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A Neuroleptic drug targets Brain-eating Amoeba: Effects of Promethazine on Neurotropic Acanthamoeba castellanii.

08:00 EDT 12th April 2019 | BioPortfolio

Summary of "A Neuroleptic drug targets Brain-eating Amoeba: Effects of Promethazine on Neurotropic Acanthamoeba castellanii."

Acanthamoeba spp. has recently been reported to express diverse group of ion-channels and receptors that are expressed by human cells which bind drugs that are used in non-infectious diseases. Bioinformatics computational tools, growth assays and 3D structural modeling has enabled the discovery of primitive muscarinic receptors, voltage gated calcium channels and transport pumps like Na-K ATPase in this protist pathogen. The significance of the reported receptors and ion-channels in the biology of Acanthamoeba is yet to be discovered. We selected Promethazine which is a known antagonist of proteins like dopaminergic, histaminergic, muscarinic receptors and calmodulin to determine its effects on the growth and proliferation of trophozoites and cysts of Acanthamoeba spp. In order to elucidate the receptors involved in the effects produced by promethazine, we also performed individual experiments on Acanthamoeba trophozoites and cysts in the presence of the agonist of the above-mentioned receptors. Our results show that promethazine in a range of 60-100µg/ml proved to be amoebicidal for Acanthamoeba trophozoites and at slightly higher doses 125-250 µg/ml also showed partial cysticidal effects. We also show the evidence of homology between the human targets of promethazine and similar targets in Acanthamoeba by the use of bioinformatic computational tools and 3D modeling. Promethazine and its structural analogs, because of being FDA approved and having a wider margin of safety that can be tested as potential anti-Acanthamoeba agents in diseases like keratitis and encephalitis caused by this protist pathogen.

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Name: ACS chemical neuroscience
ISSN: 1948-7193
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