针对布鲁氏锥虫和其他锥虫的核苷酸代谢。

IF 10.1 2区 生物学 Q1 MICROBIOLOGY
Anders Hofer
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引用次数: 2

摘要

非洲昏睡病、恰加斯病和利什曼病是危及生命的疾病,它们共同影响着全世界数百万人,由原生动物科锥虫科的不同成员引起。该家族中研究最多的成员是布鲁氏锥虫,它由采采蝇传播并引起非洲昏睡病。布鲁氏锥虫和其他锥虫的核苷酸代谢与哺乳动物明显不同,早在20世纪70- 80年代就被认为是化疗的靶点。近年来,对核苷酸代谢的更彻底的研究为鉴定核苷类似物铺平了道路,这些核苷类似物可以在动物模型中治愈布鲁氏杆菌脑感染。布鲁氏体核苷酸代谢的特定特征包括缺乏新的嘌呤生物合成,存在非常有效的嘌呤转运体,缺乏CTP合成的挽救途径,独特的酶定位,以及最近发现的dTTP合成的新途径。本文综述了布鲁氏锥虫的核苷酸代谢,强调了与其他锥虫的异同,并讨论了如何利用寄生虫的特异性特征进行药物开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids.

Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids.

Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids.

Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids.

African sleeping sickness, Chagas disease, and leishmaniasis are life-threatening diseases that together affect millions of people around the world and are caused by different members of the protozoan family Trypanosomatidae. The most studied member of the family is Trypanosoma brucei, which is spread by tsetse flies and causes African sleeping sickness. Nucleotide metabolism in T. brucei and other trypanosomatids is significantly different from that of mammals and was recognized as a target for chemotherapy already in the 1970-1980s. A more thorough investigation of the nucleotide metabolism in recent years has paved the way for identifying nucleoside analogues that can cure T. brucei brain infections in animal models. Specific features of T. brucei nucleotide metabolism include the lack of de novo purine biosynthesis, the presence of very efficient purine transporters, the lack of salvage pathways for CTP synthesis, unique enzyme localizations, and a recently discovered novel pathway for dTTP synthesis. This review describes the nucleotide metabolism of T. brucei, highlights differences and similarities to other trypanosomatids, and discusses how to exploit the parasite-specific features for drug development.

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来源期刊
FEMS microbiology reviews
FEMS microbiology reviews 生物-微生物学
CiteScore
17.50
自引率
0.90%
发文量
45
审稿时长
6-12 weeks
期刊介绍: Title: FEMS Microbiology Reviews Journal Focus: Publishes reviews covering all aspects of microbiology not recently surveyed Reviews topics of current interest Provides comprehensive, critical, and authoritative coverage Offers new perspectives and critical, detailed discussions of significant trends May contain speculative and selective elements Aimed at both specialists and general readers Reviews should be framed within the context of general microbiology and biology Submission Criteria: Manuscripts should not be unevaluated compilations of literature Lectures delivered at symposia must review the related field to be acceptable
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