Kumar Rajender, Sharma Parvati, Kumar Gaur Deepak, Jain Shikha
ICAR- National Research Centre on Equines, Sirsa Road, Hisar-125001 (Haryana), India.
Curr Top Med Chem. 2016;16(20):2303-15. doi: 10.2174/1568026616666160413125453.
Trypanosomatids continue to cause suffering among human and wide range of animal population and have enormous health, social and economic impact. The present constraints in control of trypanosomosis are availability of limited number of effective drugs with narrow safety index, nonavailability of vaccines due to immune evasion mechanisms developed by the parasite and drug resistance problem. The kinetoplastids/ trypanosomatids possess unique kinetoplast DNA structure and express hundreds of membrane transport proteins that allow them to take up nutrients, establish ion gradients, efflux metabolites, translocate compounds from one intracellular compartment to another, and take up or export drugs. In this context, there is urgent need of application of innovative strategies for identification of novel therapeutic drug targets affecting metabolic pathways essential for survival of the parasites using modern molecular approaches (functional/genomics/ proteomics/bioinformatics). In this review we have discussed existing drugs in use for treatment and outline of emerging approaches in identification and evaluation of potential novel therapeutic targets against trypanosomatids.
锥虫继续给人类和广泛的动物种群带来痛苦,并产生巨大的健康、社会和经济影响。目前控制锥虫病的制约因素包括有效药物数量有限且安全指数窄、由于寄生虫发展出的免疫逃避机制而无法获得疫苗以及耐药性问题。动质体/锥虫具有独特的动质体DNA结构,并表达数百种膜转运蛋白,这些蛋白使它们能够摄取营养物质、建立离子梯度、排出代谢产物、将化合物从一个细胞内区室转运到另一个区室,以及摄取或排出药物。在这种情况下,迫切需要应用创新策略,利用现代分子方法(功能/基因组学/蛋白质组学/生物信息学)来鉴定影响寄生虫生存所必需代谢途径的新型治疗药物靶点。在这篇综述中,我们讨论了现有的治疗药物,并概述了鉴定和评估针对锥虫的潜在新型治疗靶点的新出现方法。