'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.

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 dup...

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Autores principales:	John D Chan, Prince N Agbedanu, Mostafa Zamanian, Sarah M Gruba, Christy L Haynes, Timothy A Day, Jonathan S Marchant
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9ccdf22336a74c7a84f85be21f6a44b8
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spelling	oai:doaj.org-article:9ccdf22336a74c7a84f85be21f6a44b82021-11-18T06:06:58Z'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.1553-73661553-737410.1371/journal.ppat.1003942https://doaj.org/article/9ccdf22336a74c7a84f85be21f6a44b82014-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586156/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Schistosomiasis 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.John D ChanPrince N AgbedanuMostafa ZamanianSarah M GrubaChristy L HaynesTimothy A DayJonathan S MarchantPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 2, p e1003942 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 John D Chan Prince N Agbedanu Mostafa Zamanian Sarah M Gruba Christy L Haynes Timothy A Day Jonathan S Marchant 'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.
description	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.
format	article
author	John D Chan Prince N Agbedanu Mostafa Zamanian Sarah M Gruba Christy L Haynes Timothy A Day Jonathan S Marchant
author_facet	John D Chan Prince N Agbedanu Mostafa Zamanian Sarah M Gruba Christy L Haynes Timothy A Day Jonathan S Marchant
author_sort	John D Chan
title	'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.
title_short	'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.
title_full	'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.
title_fullStr	'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.
title_full_unstemmed	'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.
title_sort	'death and axes': unexpected ca²⁺ entry phenologs predict new anti-schistosomal agents.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/9ccdf22336a74c7a84f85be21f6a44b8
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'Death and axes': unexpected Ca²⁺ entry phenologs predict new anti-schistosomal agents.

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