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血吸虫寄生虫的氧化还原生物学及其在药物开发中的应用。

The redox biology of schistosome parasites and applications for drug development.

机构信息

Department of Microbiology and Immunology, Rush University Medical Center, Chicago, IL 60612-3824, USA.

出版信息

Curr Pharm Des. 2012;18(24):3595-611.

Abstract

Schistosomiasis caused by Schistosoma spp. is a serious public health concern, especially in sub-Saharan Africa. Praziquantel is the only drug currently administrated to treat this disease. However, praziquantel-resistant parasites have been identified in endemic areas and can be generated in the laboratory. Therefore, it is essential to find new therapeutics. Antioxidants are appealing drug targets. In order to survive in their hosts, schistosomes are challenged by reactive oxygen species from intrinsic and extrinsic sources. Schistosome antioxidant enzymes have been identified as essential proteins and novel drug targets and inhibition of the antioxidant response can lead to parasite death. Because the organization of the redox network in schistosomes is significantly different from that in humans, new drugs are being developed targeting schistosome antioxidants. In this paper the redox biology of schistosomes is discussed and their potential use as drug targets is reviewed. It is hoped that compounds targeting parasite antioxidant responses will become clinically relevant drugs in the near future.

摘要

由血吸虫属引起的血吸虫病是一个严重的公共卫生问题,特别是在撒哈拉以南非洲地区。目前,吡喹酮是唯一用于治疗这种疾病的药物。然而,在流行地区已经发现了对吡喹酮有抗药性的寄生虫,并且可以在实验室中产生。因此,寻找新的治疗方法至关重要。抗氧化剂是一种有吸引力的药物靶点。为了在宿主中生存,血吸虫受到来自内在和外在来源的活性氧的挑战。血吸虫抗氧化酶已被确定为必需蛋白和新的药物靶点,抑制抗氧化反应可导致寄生虫死亡。由于血吸虫体内的氧化还原网络的组织与人类有很大的不同,因此正在针对血吸虫抗氧化剂开发新药。本文讨论了血吸虫的氧化还原生物学,并综述了其作为药物靶点的潜在用途。希望针对寄生虫抗氧化反应的化合物在不久的将来能成为临床上相关的药物。

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