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Egg-laying and locomotory screens with C. elegans yield a nematode-selective small molecule stimulator of neurotransmitter release
- Publication Year :
- 2022
- Publisher :
- University of Basel, 2022.
-
Abstract
- Nematode parasites of humans, livestock and crops dramatically impact human health and welfare. Alarmingly, parasitic nematodes of animals have rapidly evolved resistance to anthelmintic drugs, and traditional nematicides that protect crops are facing increasing restrictions because of poor phylogenetic selectivity. Here, we exploit multiple motor outputs of the model nematode C. elegans towards nematicide discovery. This work yielded multiple compounds that selectively kill and/or immobilize diverse nematode parasites. We focus on one compound that induces violent convulsions and paralysis that we call nementin. We find that nementin stimulates neuronal dense core vesicle release, which in turn enhances cholinergic signaling. Consequently, nementin synergistically enhances the potency of widely- used non-selective acetylcholinesterase (AChE) inhibitors, but in a nematode-selective manner. Nementin therefore has the potential to reduce the environmental impact of toxic AChE inhibitors that are used to control nematode infections and infestations. A C. elegans-based screening approach identifies nementin as a nematode- selective nematicide that can be used synergistically with acetylcholinesterase inhibitors
- Subjects :
- Neurotransmitter Agents
Nematoda
Antinematodal Agents
Acetylcholinesterase
Animals
Humans
Medicine (miscellaneous)
Caenorhabditis elegans
General Agricultural and Biological Sciences
Phylogeny
CAENORHABDITIS-ELEGANS
NIPPOSTRONGYLUS-BRASILIENSIS
ACETYLCHOLINESTERASE
G(Q)ALPHA
HELMINTHS
GENETICS
PATHWAY
CHANNEL
VESICLE
CAPS
General Biochemistry, Genetics and Molecular Biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c4caa5211d562c1e8107e181cb2cbb9d
- Full Text :
- https://doi.org/10.5451/unibas-ep90530