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Neurotransmitter transporters in schistosomes: structure, function and prospects for drug discovery.
- Source :
-
Parasitology international [Parasitol Int] 2013 Dec; Vol. 62 (6), pp. 629-38. Date of Electronic Publication: 2013 Jun 22. - Publication Year :
- 2013
-
Abstract
- Neurotransmitter transporters (NTTs) play a fundamental role in the control of neurotransmitter signaling and homeostasis. Sodium symporters of the plasma membrane mediate the cellular uptake of neurotransmitter from the synaptic cleft, whereas proton-driven vesicular transporters sequester the neurotransmitter into synaptic vesicles for subsequent release. Together these transporters control how much transmitter is released and how long it remains in the synaptic cleft, thereby regulating the intensity and duration of signaling. NTTs have been the subject of much research in mammals and there is growing interest in their activities among invertebrates as well. In this review we will focus our attention on NTTs of the parasitic flatworm Schistosoma mansoni. Bloodflukes of the genus Schistosoma are the causative agents of human schistosomiasis, a devastating disease that afflicts over 200 million people worldwide. Schistosomes have a well-developed nervous system and a rich diversity of neurotransmitters, including many of the small-molecule ("classical") neurotransmitters that normally employ NTTs in their mechanism of signaling. Recent advances in schistosome genomics have unveiled numerous NTTs in this parasite, some of which have now been cloned and characterized in vitro. Moreover new genetic and pharmacological evidence suggests that NTTs are required for proper control of neuromuscular signaling and movement of the worm. Among these carriers are proteins that have been successfully targeted for drug discovery in other organisms, in particular sodium symporters for biogenic amine neurotransmitters such as serotonin and dopamine. Our goal in this chapter is to review the current status of research on schistosome NTTs, with emphasis on biogenic amine sodium symporters, and to evaluate their potential for anti-schistosomal drug targeting. Through this discussion we hope to draw attention to this important superfamily of parasite proteins and to identify new directions for future research.<br /> (© 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Cluster Analysis
Dopamine Plasma Membrane Transport Proteins classification
Dopamine Plasma Membrane Transport Proteins genetics
Dopamine Plasma Membrane Transport Proteins metabolism
Drug Discovery
Genomics
Helminth Proteins classification
Helminth Proteins genetics
Helminth Proteins metabolism
Homeostasis drug effects
Humans
Neurotransmitter Transport Proteins classification
Neurotransmitter Transport Proteins genetics
RNA Interference
Schistosoma mansoni drug effects
Schistosoma mansoni genetics
Schistosomiasis mansoni drug therapy
Serotonin Plasma Membrane Transport Proteins classification
Serotonin Plasma Membrane Transport Proteins genetics
Serotonin Plasma Membrane Transport Proteins metabolism
Signal Transduction drug effects
Biogenic Amines metabolism
Neurotransmitter Agents metabolism
Neurotransmitter Transport Proteins metabolism
Schistosoma mansoni metabolism
Schistosomiasis mansoni parasitology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-0329
- Volume :
- 62
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Parasitology international
- Publication Type :
- Academic Journal
- Accession number :
- 23800409
- Full Text :
- https://doi.org/10.1016/j.parint.2013.06.003