Strategies for the Identification of Bioactive Neuropeptides in Vertebrates

Abstract

Neuropeptides exert essential functions in animal physiology by controlling e.g., reproduction, development, growth, energy homeostasis, cardiovascular activity and stress response. Thus, identification of neuropeptides has been a very active field of research over the last decades. This review article presents the various methods used to discover novel bioactive peptides in vertebrates. Initially identified on the basis of their biological activity, some neuropeptides have also been discovered for their ability to bind/activate a specific receptor or based on their biochemical characteristics such as C-terminal amidation which concerns half of the known neuropeptides. More recently, sequencing of the genome of many representative species has facilitated peptidomic approaches using mass spectrometry and in silico screening of genomic libraries. Through these different approaches, more than a hundred of bioactive neuropeptides have already been identified in vertebrates. Nevertheless, researchers continue to find new neuropeptides or to identify novel functions of neuropeptides that had not been detected previously, as it was recently the case for nociceptin.

Ion Mobility Coupled to a Time-of-Flight Mass Analyzer Combined With Fragment Intensity Predictions Improves Identification of Classical Bioactive Peptides and Small Open Reading Frame-Encoded Peptides

“…For example, a CRISPR-based screening strategy revealed an essential biological function for hundreds of non-canonical coding sequences in human cells (Chen et al, 2020). Besides knock-out or knock downs of the precursor protein to evaluate biological effect, the bioactivity of neuropeptides can be assessed by specific assays (reviewed in Corbière et al, 2019). A recent study (Palkeeva et al, 2019) generated structural analogues of Galanin peptides to investigate the biological activity of new forms in comparison to previously described ones.…”

Peptidome: Chaos or Inevitability

“…For example, subtilase S1P (SITE 1 PROTEASE)/SBT6.1 is responsible for the biogenesis of the RGF/GLV/CLEL and RALF peptide hormones in plants [ 77 ]. In mammals, seven subtilisin/kexin-like endoproteases named prohormone convertases (PCs) are responsible for the release of neuropeptides [ 78 ]. Precursors of human growth factors are reported to be embedded in the membranes of vesicles and bioactive peptides can be released by extracellular proteases, such as serine proteases, upon the merging of vesicles with plasma membranes [ 79 ].…”

Identification, Characterization, and Expression of a PRQFVamide-Related Peptide in Cephalopod Sepiella japonica

“…Neuropeptides are signaling molecular produced and released primarily by neurons and engaged in diverse physiological processes (Wang et al, 2015). A large number of bioactive neuropeptides have been found in vertebrates with multiple functions in the regulation of learning and memory, reproduction, energy homeostasis, cardiovascular activity, and stress response (Corbière et al, 2019). Since the first neuropeptide eledoisin was sequenced from octopus Eledone moschata (Erspamer and Anastasi, 1962), neuropeptides have been extensively studied in multiple invertebrates, including mollusks (Price and Greenberg, 1977;Pulst et al, 1988), nematodes (Davenport et al, 1988;Keating et al, 1995), and arthropods (Marder et al, 1986;Nambu et al, 1988).…”