Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems.
Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human diseases. Graphical Abstract ᅟ.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093-0719, USA. vhook@ucsd.edu.|School of Medicine, Department of Neurosciences and Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093-0719, USA. vhook@ucsd.edu.
Vivian
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Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093-0719, USA.|Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, 92093-0719, USA.
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Bandeira
D000595:Amino Acid Sequence; D002403:Cathepsins / Q000032:analysis / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000378:metabolism; D004745:Enkephalins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D053858:Metabolic Networks and Pathways; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000032:analysis / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D022142:Secretory Vesicles / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
D004745:Enkephalins; D009479:Neuropeptides; D002403:Cathepsins; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C117627:CTSV protein, human
Bioinformatics; Biomarker; Cathepsin L; Cathepsin V; Drug response; Human signaling networks; Intercellular signaling; Neuropeptidomics; Neurotransmitters; Peptide hormones; Proprotein convertase; Protease cleavage sites; Proteases; Proteomics; Secretory vesicles