‘Death and Axes’: Unexpected Ca2+ Entry Phenologs Predict New Anti-schistosomal Agents

PLoS Pathogens

Timothy A. Day¹  Prince N. Agbedanu¹  Mostafa Zamanian¹  Christy L. Haynes²  Sarah M. Gruba²  John D. Chan³  Jonathan S. Marchant³ 

[1] Department of Biomedical Sciences, Iowa State University, Ames, Iowa, United States of America;Department of Chemistry, University of Minnesota, Minneapolis, Minnesota, United States of America;Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America

关键词: Planarians;    Dopaminergics;    Schistosoma;    RNA interference;    Drug screening;    Flatworms;    Dopamine;    Head regeneration;   

DOI  :  10.1371/journal.ppat.1003942

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY