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核受体:寄生虫病新出现的药物靶点

Nuclear receptors: emerging drug targets for parasitic diseases.

作者信息

Wang Zhu, Schaffer Nathaniel E, Kliewer Steven A, Mangelsdorf David J

出版信息

J Clin Invest. 2017 Apr 3;127(4):1165-1171. doi: 10.1172/JCI88890. Epub 2017 Feb 6.

Abstract

Parasitic worms infect billions of people worldwide. Current treatments rely on a small group of drugs that have been used for decades. A shortcoming of these drugs is their inability to target the intractable infectious stage of the parasite. As well-known therapeutic targets in mammals, nuclear receptors have begun to be studied in parasitic worms, where they are widely distributed and play key roles in governing metabolic and developmental transcriptional networks. One such nuclear receptor is DAF-12, which is required for normal nematode development, including the all-important infectious stage. Here we review the emerging literature that implicates DAF-12 and potentially other nuclear receptors as novel anthelmintic targets.

摘要

寄生虫感染了全球数十亿人。目前的治疗方法依赖于一小类已使用数十年的药物。这些药物的一个缺点是它们无法靶向寄生虫难以治疗的感染阶段。作为哺乳动物中众所周知的治疗靶点,核受体已开始在寄生虫中得到研究,它们在寄生虫中广泛分布,并在调控代谢和发育转录网络中发挥关键作用。其中一种核受体是DAF-12,它是正常线虫发育所必需的,包括至关重要的感染阶段。在此,我们综述了一些新出现的文献,这些文献表明DAF-12以及其他可能的核受体是新型抗蠕虫药物的靶点。

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本文引用的文献

1
Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections.
PLoS Negl Trop Dis. 2016 Jun 14;10(6):e0004772. doi: 10.1371/journal.pntd.0004772. eCollection 2016 Jun.
2
Regulation of Life Cycle Checkpoints and Developmental Activation of Infective Larvae in Strongyloides stercoralis by Dafachronic Acid.
PLoS Pathog. 2016 Jan 4;12(1):e1005358. doi: 10.1371/journal.ppat.1005358. eCollection 2016 Jan.
3
Nuclear receptor signal transduction in C. elegans.
WormBook. 2015 Jun 9:1-49. doi: 10.1895/wormbook.1.64.2.
5
The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes.
PLoS Genet. 2015 Mar 16;11(3):e1005027. doi: 10.1371/journal.pgen.1005027. eCollection 2015 Mar.
6
Ecdysone response gene E78 controls ovarian germline stem cell niche formation and follicle survival in Drosophila.
Dev Biol. 2015 Apr 1;400(1):33-42. doi: 10.1016/j.ydbio.2015.01.013. Epub 2015 Jan 23.
7
Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans.
Science. 2015 Jan 2;347(6217):83-6. doi: 10.1126/science.1258857.
8
Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans.
WormBook. 2014 Dec 16:1-29. doi: 10.1895/wormbook.1.143.2.
9
Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans.
PLoS Genet. 2014 Dec 4;10(12):e1004829. doi: 10.1371/journal.pgen.1004829. eCollection 2014 Dec.
10
A lophotrochozoan-specific nuclear hormone receptor is required for reproductive system development in the planarian.
Dev Biol. 2014 Dec 1;396(1):150-7. doi: 10.1016/j.ydbio.2014.09.024. Epub 2014 Sep 30.

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