[
1992]
In vertebrates, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are polymorphic enzymes presenting both globular and asymmetric forms. In invertebrates, only AChE has been characterized so far that presents a reduced molecular diversity. In insects for example the major molecular form of AChE is an amphiphilic dimeric form attached to the membrane through a glycolipid covalently linked at the C-terminus of each catalytic subunit. This AChE has a substrate specificity intermediate to those of mammalina AChE and BChE. A glycoplipid-anchored 7.5S from has also been observed in the trematode Schistosoma mansoni. Asymmetric forms have never been convincingly reported in invertebrates except in the more evolved animals such as Amphioxius. In the latter case also there is no BChE but AChE presents catalytic properties intermediate to those of vertebrate AChE and BChE. We are now interested in nematode AChE(s) for the following reasons: -several species are agricultural pest and it is important to get further informations on the target of potential nematicides; -it has been shown that at least three different genes code for AChE in Caenorhabditis elegans. It is therefore interesting to see whether the presence of multiple genes results in an increased molecular diversity, to define what are the structural characteristics of each gene product and finally to clone and sequence thee three genes for evolutionary relationships with the other members of the cholinesterase
[
Adv Exp Med Biol,
2010]
Nematode neuropeptide systems comprise an exceptionally complex array of approximately 250 peptidic signaling molecules that operate within a structurally simple nervous system of approximately 300 neurons. A relatively complete picture of the neuropeptide complement is available for Caenorhabditis elegans, with 30 flp, 38 ins and 43 nlp genes having been documented; accumulating evidence indicates similar complexity in parasitic nematodes from clades I, III, IV and V. In contrast, the picture for parasitic platyhelminths is less clear, with the limited peptide sequence data available providing concrete evidence for only FMRFamide-like peptide (FLP) and neuropeptide F (NPF) signaling systems, each of which only comprises one or two peptides. With the completion of the Schmidtea meditteranea and Schistosoma mansoni genome projects and expressed sequence tag datasets for other flatworm parasites becoming available, the time is ripe for a detailed reanalysis ofneuropeptide signalingin flatworms. Although the actual neuropeptides provide limited obvious value as targets for chemotherapeutic-based control strategies, they do highlight the signaling systems present in these helminths and provide tools for the discovery of more amenable targets such as neuropeptide receptors or neuropeptide processing enzymes. Also, they offer opportunities to evaluate the potential of their associated signaling pathways as targets through RNA interference (RNAi)-based, target validation strategies. Currently, within both helminth phyla, theflp signaling systems appear to merit further investigation as they are intrinsically linked with motor function, a proven target for successful anti-parasitics; it is clear that some nematode NLPs also play a role in motor function and could have similar appeal. At this time, it is unclear if flatworm NPF and nematode INS peptides operate in pathways that have utility for parasite control. Clearly, RNAi-based validation could be a starting point for scoring potential target pathways within neuropeptide signaling for parasiticide discovery programs. Also, recent successes in the application of in planta-based RNAi control strategies for plant parasitic nematodes reveal a strategy whereby neuropeptide encoding genes could become targets for parasite control. The possibility of developing these approaches for the control of animal and human parasites is intriguing, but will require significant advances in the delivery of RNAi-triggers.