Nuclear receptors: emerging drug targets for parasitic diseases
Zhu Wang, … , Steven A. Kliewer, David J. Mangelsdorf
Zhu Wang, … , Steven A. Kliewer, David J. Mangelsdorf
Published April 3, 2017; First published February 6, 2017
Citation Information: J Clin Invest. 2017;127(4):1165-1171. https://doi.org/10.1172/JCI88890.
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Review Series

Nuclear receptors: emerging drug targets for parasitic diseases

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.

Authors

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

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Figure 1

The DAF-12 signaling pathway.

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The DAF-12 signaling pathway. (A) Under favorable environmental conditio...
(A) Under favorable environmental conditions, the free-living nematode C. elegans stimulates the production of steroid-like hormones (i.e., DAs) that activate the DAF-12 nuclear receptor. DAF-12 activation results in transcription of a metabolic and development gene network that promotes reproductive maturity. (B) In unfavorable conditions when DAs are not synthesized, DAF-12 functions as a transcriptional repressor of this gene network that results in developmental arrest and entry into the dauer diapause. In helminthic nematodes, this same pathway is believed to govern the development of infectious larvae and the resumption of their development into reproductive maturity after entering their hosts.