Schistosome ABC multidrug transporters: From pharmacology to physiology.
Schistosome ABC multidrug transporters: From pharmacology to physiology.
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DOI：
10.1016/j.ijpddr.2014.09.007
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发表时间：
2014-12
影响因子：
4
通讯作者：
Greenberg, Robert M.
中科院分区：
文献类型：
--
作者：
Greenberg, Robert M.
关键词：
对血吸虫ABC转运蛋白的真实作用和假想作用进行了综述。对转运蛋白在血吸虫药物敏感性中的作用的证据进行了讨论。概述了ABC转运蛋白在正常血吸虫生物学中的潜在作用。吡喹酮(PZQ)基本上是目前可用于治疗和控制血吸虫病的唯一药物，血吸虫病是一种影响全球数亿人的疾病。尽管PZQ总体上非常有效，但它也有局限性，最明显的是它对未成熟的血吸虫缺乏活性。此外，对于这种规模的疾病，只有一种药物可用，这使得有关PZQ耐药菌株的报告特别令人担忧。ATP结合盒(ABC)多药转运蛋白如P-糖蛋白(Pgp；ABCB1)是构成多药耐药(MDR)的外排转运蛋白；其表达或结构的变化也与寄生虫(包括蠕虫)的耐药性有关。这篇综述将讨论这些转运蛋白在调节血吸虫对PZQ的易感性中可能发挥的作用，以及开发新的或重新定位的治疗方法以增强PZQ的疗效的意义。然而，除了影响药物敏感性外，ABC转运蛋白在排泄和维持通透性屏障等几个关键生理功能中也发挥着重要作用。它们还以高亲和力运输信号分子，有几条证据表明哺乳动物的转运蛋白参与了一系列不同的生理功能，包括免疫反应的调节。与哺乳动物一样，血吸虫ABC转运蛋白似乎参与了对寄生虫至关重要的功能，包括排泄活动和繁殖，我们假设它们至少是寄生虫与宿主相互作用的某些方面的基础。因此，除了它们作为PZQ易感性增强剂的潜在靶点外，这些转运体也可能成为扰乱寄生虫生命周期并作为自身抗血吸虫药物的候选靶点。
The genuine and hypothesized roles of schistosome ABC transporters are reviewed. Evidence suggesting a role for transporters in schistosome drug susceptibility is discussed. Potential roles of ABC transporters in normal schistosome biology are outlined. Praziquantel (PZQ) is essentially the only drug currently available for treatment and control of schistosomiasis, a disease affecting hundreds of millions worldwide. Though highly effective overall, PZQ has limitations, most notably its significant lack of activity against immature schistosomes. Furthermore, the availability of only a single drug for a disease of this magnitude makes reports of PZQ-resistant isolates particularly troubling. ATP-binding cassette (ABC) multidrug transporters such as P-glycoprotein (Pgp; ABCB1) are efflux transporters that underlie multidrug resistance (MDR); changes in their expression or structure are also associated with drug resistance in parasites, including helminths. This review will discuss the role these transporters might play in modulating schistosome susceptibility to PZQ, and the implications for developing new or repurposed treatments that enhance the efficacy of PZQ. However, in addition to influencing drug susceptibility, ABC transporters play important roles in several critical physiological functions such as excretion and maintenance of permeability barriers. They also transport signaling molecules with high affinity, and several lines of evidence implicate mammalian transporters in a diverse array of physiological functions, including regulation of immune responses. Like their mammalian counterparts, schistosome ABC transporters appear to be involved in functions critical to the parasite, including excretory activity and reproduction, and we hypothesize that they underlie at least some aspects of parasite–host interactions. Thus, in addition to their potential as targets for enhancers of PZQ susceptibility, these transporters might also serve as candidate targets for agents that disrupt the parasite life cycle and act as antischistosomals on their own.
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DOI：
10.1007/978-1-60761-416-6_15
发表时间：
2010-01-01
期刊：
MULTI-DRUG RESISTANCE IN CANCER
影响因子：
--
作者：
Coley, Helen M.
通讯作者：
Coley, Helen M.
DOI：
10.1126/science.1168750
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Aller SG;Yu J;Ward A;Weng Y;Chittaboina S;Zhuo R;Harrell PM;Trinh YT;Zhang Q;Urbatsch IL;Chang G
通讯作者：
Chang G
影响因子：
4.8
作者：
Aksoy, E;Zouain, CS;Trottein, F
通讯作者：
Trottein, F
影响因子：
4.2
作者：
Chai JY
通讯作者：
Chai JY
影响因子：
2
作者：
Cioli, D;Pica-Mattoccia, L
通讯作者：
Pica-Mattoccia, L