title: Parasite neuropeptide biology: Seeding rational drug target selection?
abstract: The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components - putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths.
authors.affiliation: Molecular Biosciences-Parasitology, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: McVeigh
authors.affiliation: Molecular Biosciences-Parasitology, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Atkinson
authors.affiliation: Molecular Biosciences-Parasitology, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Nikki J
authors.initials: NJ
authors.lastname: Marks
authors.affiliation: Molecular Biosciences-Parasitology, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Mousley
authors.affiliation: Molecular Biosciences-Parasitology, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Johnathan J
authors.initials: JJ
authors.lastname: Dalzell
authors.affiliation: Scynexis Inc., P.O. Box 12878, Research Triangle Park, NC 27709-2878, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Sluder
authors.affiliation: Merial Limited, 3239 Satellite Blvd., Duluth, GA 30096, USA.
authors.forename: Lance
authors.initials: L
authors.lastname: Hammerland
authors.affiliation: Molecular Biosciences-Parasitology, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Maule
keywords: Anthelmintic; Nervous system; Neuromuscular; Receptor; Signalling