Discovery of multiple neuropeptide families in the phylum Platyhelminthes

Abstract

Available evidence shows that short amidated neuropeptides are widespread and have important functions within the nervous systems of all flatworms (phylum Platyhelminthes) examined, and could therefore represent a starting point for new lead drug compounds with which to combat parasitic helminth infections. However, only a handful of these peptides have been characterised, the rigorous exploration of the flatworm peptide signalling repertoire having been hindered by the dearth of flatworm genomic data. Through searches of both expressed sequence tags and genomic resources using the basic local alignment search tool (BLAST), we describe 96 neuropeptides on 60 precursors from 10 flatworm species. Most of these (51 predicted peptides on 14 precursors) are novel and are apparently restricted to flatworms; the remainder comprise nine recognised peptide families including FMRFamide-like (FLPs), neuropeptide F (NPF)-like, myomodulin-like, buccalin-like and neuropeptide FF (NPFF)-like peptides; notably, the latter have only previously been reported in vertebrates. Selected peptides were localised immunocytochemically to the Schistosoma mansoni nervous system. We also describe several novel flatworm NPFs with structural features characteristic of the vertebrate neuropeptide Y (NPY) superfamily, previously unreported characteristics which support the common ancestry of flatworm NPFs with the NPY-superfamily. Our dataset provides a springboard for investigation of the functional biology and therapeutic potential of neuropeptides in flatworms, simultaneously launching flatworm neurobiology into the post-genomic era.

Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

“…Other drugs that have been used in the treatment of schistosomiasis are oxamniquine (vansil) for S. mansoni and metrifonate (trichlorfon) for S. haematobium, but both are ineffective against S. japonicum. Potential new targets for drug development against schistosomes include peroxiredoxin-1 (110), thioredoxin glutathione reductase (174), tyrosine kinases (183), tyrosine kinase receptors (4, 5), phosphatidylinositol kinases (11), and neuropeptides (141).…”

A review of FMRFamide- and RFamide-like peptides in metazoa

“…This suggests that all three FLPs act on a common FLP receptor on turbellarian muscle. Recently using ESTs and BLAST searches, a number of putative RFas have been identified in platyhelminths from neuropeptide precursor genes, Table 2 (McVeigh et al 2009). In addition, these authors have identified RYamides, RWamides, Wamides, Famides and two tripeptides, NYFa and NYYa (both from Dugesia japonica).…”

Protein Based Drug Discovery

“…Ternatin also inhibited triglyceride synthesis in rat primary hepatocytes, suggesting that the potential action sites for ternatin are shared by adipocytes and liver [75]. Short amidated neuropeptides are widespread have important functions within the nervous systems of all flatworms (phylum Platyhelminthes) examined, and could therefore represent a starting point for new lead drug compounds with which to combat parasitic helminth infections [76]. Protein transduction domain (PTD)-peptides greatly facilitate the delivery of high molecular weight macromolecules across the blood-brain barrier (BBB).…”