Neurotransmitter transporters in schistosomes: Structure, function and prospects for drug discovery

Ribeiro, Paula; Patocka, Nicholas

doi:10.1016/j.parint.2013.06.003

Cited by 31 publications

(31 citation statements)

References 92 publications

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“…For example, neurotransmitter transporters, which translocate neurotransmitters across membranes, are critical for regulating neurotransmission, are validated drug targets in human medicine, and are critical to normal neuronal functioning in helminths [89]. GPCRs play essential roles in signal transduction, and are estimated to be molecular targets for more than 30% of current drugs [90].…”

Section: Related Targetsmentioning

confidence: 99%

Ion Channels and Drug Transporters as Targets for Anthelmintics

Greenberg

2014

Curr Clin Micro Rpt

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Infections with parasitic helminths such as schistosomes and soil-transmitted nematodes are hugely prevalent and responsible for a major portion of the global health and economic burdens associated with neglected tropical diseases. In addition, many of these parasites infect livestock and plants used in agriculture, resulting in further impoverishment. Treatment and control of these pathogens rely on anthelmintic drugs, which are few in number, and against which drug resistance can develop rapidly. The neuromuscular system of the parasite, and in particular, the ion channels and associated receptors underlying excitation and signaling, have proven to be outstanding targets for anthelmintics. This review will survey the different ion channels found in helminths, focusing on their unique characteristics and pharmacological sensitivities. It will also briefly review the literature on helminth multidrug efflux that may modulate parasite susceptibility to anthelmintics and may prove useful targets for new or repurposed agents that can enhance parasite drug susceptibility and perhaps overcome drug resistance.

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Section: Related Targetsmentioning

confidence: 99%

Ion Channels and Drug Transporters as Targets for Anthelmintics

Greenberg

2014

Curr Clin Micro Rpt

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“…3J, K, M). HT/dopamine across the tegument (Ribeiro and Patocka, 2013). Therefore, given the 289 tegumental and neural localization of activated PKA in somules and the effects of forskolin 290 on somule movement observed here, we hypothesized that these BAs might modulate 291 PKA activation in somules.…”

Section: In Situ Distribution Of Activated Pka and Pka-preferred Submentioning

confidence: 87%

Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules

Hirst

Lawton

Walker

2016

International Journal for Parasitology

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Please cite this article as: Hirst, N.L., Lawton, S.P., Walker, A.J., Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules, International Journal for Parasitology (2016), doi: http://dx.doi.org/ 10.1016/j.ijpara. 2015.12.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Platyhelminthes appear to lack a conventional endocrine system [38], and are therefore heavily reliant on neural signalling via neuropeptides that control vital dynamic physiological and neural functions, such as growth, reproduction, host-seeking olfaction, locomotion, immune evasion and sexual dimorphism [61]. The importance of their peptidergic neural and associated receptor systems holds a promising area of research for new anthelmintic drug targets [16, 62, 63]. …”

Section: Discussionmentioning

confidence: 99%

GPCR and IR genes in Schistosoma mansoni miracidia

et al. 2016

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Background Schistosoma species are responsible for the disease schistosomiasis, a highly prevalent helminthic disease that requires a freshwater snail as intermediate host. The S. mansoni free-living miracidium must utilize olfaction to find a suitable snail host, and certain types of rhodopsin G protein-coupled receptors (GPCRs) and ionotropic receptors (IRs) have been identified as olfactory receptors in other animal phyla. The Schistosoma genome project, together with the recent availability of proteomic databases, allowed for studies to explore receptors within S. mansoni, some of which may contribute to host finding.ResultsWe have identified 17 rhodopsin-type GPCR sequences in S. mansoni belonging to four subclasses, including ligand-specific GPCRs (i.e. neuropeptide and opsin). RT-PCR demonstrated the expression of nine out of the 17 GPCRs in the free-living miracidia, each of which have been characterized for homology to S. haematobium. Among the nine GPCRs, two are predicted as Gq-opsins. We also describe the characterization of a Schistosoma-encoded IR based on similarity with other species IR and conservation of IR-like domains. Schistosoma mansoni IR is expressed in miracidia at 3 and 6 h post-hatch.ConclusionsThe identification of receptors in S. mansoni miracidia, presented here, contributes not only to further understanding of Schistosoma biology and signal transduction but also provides a basis for approaches that may modify parasite behaviour.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1837-2) contains supplementary material, which is available to authorized users.

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Neurotransmitter transporters in schistosomes: Structure, function and prospects for drug discovery

Cited by 31 publications

References 92 publications

Ion Channels and Drug Transporters as Targets for Anthelmintics

Ion Channels and Drug Transporters as Targets for Anthelmintics

Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules

GPCR and IR genes in Schistosoma mansoni miracidia

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