'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents. PLoS Pathog 2014 Feb;10(2):e1003942
Date
03/04/2014Pubmed ID
24586156Pubmed Central ID
PMC3930560DOI
10.1371/journal.ppat.1003942Scopus ID
2-s2.0-84895771129 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
Schistosomiasis is a parasitic flatworm disease that infects 200 million people worldwide. The drug praziquantel (PZQ) is the mainstay therapy but the target of this drug remains ambiguous. While PZQ paralyses and kills parasitic schistosomes, in free-living planarians PZQ caused an unusual axis duplication during regeneration to yield two-headed animals. Here, we show that PZQ activation of a neuronal Ca²⁺ channel modulates opposing dopaminergic and serotonergic pathways to regulate 'head' structure formation. Surprisingly, compounds with efficacy for either bioaminergic network in planarians also displayed antischistosomal activity, and reciprocally, agents first identified as antischistocidal compounds caused bipolar regeneration in the planarian bioassay. These divergent outcomes (death versus axis duplication) result from the same Ca²⁺ entry mechanism, and comprise unexpected Ca²⁺ phenologs with meaningful predictive value. Surprisingly, basic research into axis patterning mechanisms provides an unexpected route for discovering novel antischistosomal agents.
Author List
Chan JD, Agbedanu PN, Zamanian M, Gruba SM, Haynes CL, Day TA, Marchant JSAuthor
Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBody Patterning
Calcium Channels
Chromatography, High Pressure Liquid
Planarians
Praziquantel
RNA Interference
Schistosoma
Schistosomiasis
Schistosomicides
