Neuropeptides: Chemical Activity Profiling and Proteomic Approaches

Abstract

Peptide neurotransmitters and peptide hormones, collectively known as neuropeptides, are required for cell–cell communication in neurotransmission and for regulation of endocrine functions. Neuropeptides are synthesized from protein precursors (termed proneuropeptides or prohormones) that require proteolytic processing within secretory vesicles that store and secrete active neuropeptides. This article describes the application of chemical biological approaches advantageously used to define protease pathways involved in neuropeptide biosynthesis. Activity profiling of proteases, combined with mass spectrometry, has allowed identification of the novel cathepsin L cysteine protease pathway for neuropeptide biosynthesis, which contributes to neuropeptide production with the subtilisin‐like prohormone convertase pathway. Furthermore, proteomic approaches for identifying proteases and protein systems present in secretory vesicles define the protease pathways and the functional protein systems that jointly operate in the secretory vesicle for production and secretion of active neuropeptides. Neuropeptidomic approaches allow defined primary structural analyses of neuropeptides. Future studies that gain understanding of protease mechanisms for generating active neuropeptides will be instrumental for translational research to develop therapeutic strategies for health and disease.

Neuropeptidomics of the Rat Habenular Nuclei

“…The development of modern mass spectrometry (MS) techniques, aided by improvements in sample preparation methods, have changed the way peptide detection, identification, and quantitation are performed, allowing characterization of a fairly complete set of neuropeptides present in a biological structure. − In the past decade, hundreds of neuropeptides have been discovered and identified from a range of animals using matrix-assisted laser desorption/ionization (MALDI) MS and electrospray ionization (ESI) MS. ,,− …”