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Targeting CNS Related Protist Pathogens: Calcium Ion Dependency in the Brain-Eating Amoebae.
ACS Chemical Neuroscience ( IF 5 ) Pub Date : 2019-12-16 , DOI: 10.1021/acschemneuro.9b00635
Abdul Mannan Baig 1 , Areeba Khaleeq 1 , Fizza Nazim 1
Affiliation  

Of the free-living amoebae (FLA) Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp. are known to cause encephalitis. Coined with the term “brain-eating amoebae” (BEA), infection of the central nervous system with FLA has a high mortality rate. A combination of diagnostic delay, lack of new drug development, and incomplete understanding of the dependencies of FLA have resulted in the failure of introducing safer and effective drugs. We inferred that being a shape-changing entity the FLA should have a dependency on calcium (Ca2+) ions that could be targeted to cripple the pathogenicity of the FLA. We used genomic, transcriptomic, and proteomic information available on FLA in online databases to evidence the presence of various Ca2+ion influx regulating channels, reviewing adapter proteins at first and then targeting human-like voltage-gated Ca2+ channels with nifedipine and verapamil that are used clinically for noninfectious diseases to see their effect in trophozoites of Acanthamoeba spp. in particular.

中文翻译:

靶向中枢神经系统相关的原生病原体:在大脑饮食的变形虫中的钙离子依赖性。

在自由生活的变形虫(FLA)中,Naegleria fowleriBalamuthia mandrillarisAcanthamoeba spp。已知会引起脑炎。与“食脑变形虫”(BEA)一词相称,FLA对中枢神经系统的感染具有很高的死亡率。诊断延误,缺乏新药开发以及对FLA依赖性的不完全了解,共同导致了引入更安全有效的药物的失败。我们推断,FLA作为可变形的实体,应该对钙(Ca 2+)可能会削弱FLA致病性的离子。我们使用在线数据库中FLA上可用的基因组,转录组和蛋白质组学信息来证明存在各种Ca 2+离子流入调节通道,先审查衔接蛋白,然后再用硝苯地平和类似物靶向人电压门控的Ca 2+通道。维拉帕米已在临床上用于非传染性疾病,以查看其对棘阿米巴属滋养体的作用。特别是。
更新日期:2019-12-16
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