期刊
TRENDS IN PARASITOLOGY
卷 29, 期 3, 页码 110-118出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.pt.2012.12.005
关键词
AT1; AQP2; MRPA; drug resistance; MIP; Trypanosoma brucei
类别
资金
- Wellcome Trust, the LSHTM [093010/Z/10/Z]
- Medical Research Council, the University of Glasgow [84733]
- Swiss National Science Foundation, the Swiss Tropical and Public Health Institute
- Bloomsbury colleges
- Wellcome Trust [093010/Z/10/Z] Funding Source: Wellcome Trust
- MRC [G0701258] Funding Source: UKRI
- Medical Research Council [G0701258] Funding Source: researchfish
Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over 60 years ago and remains the only example of cross-resistance among sleeping sickness therapies. A Trypanosome brucei adenosine transporter is well known for its role in the uptake of both drugs. More recently, aquaglyceroporin 2 (AQP2) loss of function was linked to melarsoprol-pentamidine cross-resistance. AQP2, a channel that appears to facilitate drug accumulation, may also be linked to clinical cases of resistance. Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites. 'Cellular therapy is a consequence of cellular nutrition, for only those compounds can affect the cell that are actually eaten by it.' - Paul Ehrlich, 1907 [1].
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