کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6136729 | 1225468 | 2013 | 10 صفحه PDF | دانلود رایگان |
Targeting the cellular Ca2Â + channels and pumps that underpin parasite Ca2Â + homeostasis may realize novel antihelmintic agents. Indeed, the antischistosomal drug praziquantel (PZQ) is a key clinical agent that has been proposed to work in this manner. Heterologous expression data has implicated an action of PZQ on voltage-operated Ca2Â + channels, although the relevant in vivo target of this drug has remained undefined over three decades of clinical use. The purpose of this review is to bring new perspective to this issue by discussing the potential utility of free-living planarian flatworms for providing new insight into the mechanism of PZQ action. First, we discuss in vivo functional genetic data from the planarian system that broadly supports the molecular data collected in heterologous systems and the 'Ca2Â + hypothesis' of PZQ action. On the basis of these similarities we highlight our current knowledge of platyhelminth voltage operated Ca2Â + channels, their unique molecular pharmacology and the downstream functional PZQ interactome engaged by dysregulation of Ca2Â + influx that has potential to yield novel antischistosomal targets. Overall the broad dataset underscores a common theme of PZQ-evoked disruptions of Ca2Â + homeostasis in trematodes, cestodes and turbellarians, and showcases the utility of the planarian model for deriving insight into drug action and targets in parasitic flatworms.
Highlights⺠The antischistosomal action of PZQ may derive from dysregulated Ca2 + homeostasis. ⺠New molecular insight supporting this model comes from the planarian model system. ⺠PZQ causes Ca2 + influx in a neuronally derived population via a specific Cav complex. ⺠The utility of the planarian model for antischistosomal drug research is discussed.
Journal: Parasitology International - Volume 62, Issue 6, December 2013, Pages 619-628