Proteases for Processing Proneuropeptides into Peptide Neurotransmitters and Hormones

Overview

Journal Annu Rev Pharmacol Toxicol

Publisher Annual Reviews

Specialties Pharmacology
Toxicology

Date 2008 Jan 11

PMID 18184105

Citations 116

Authors

Vivian Hook

Lydiane Funkelstein

Douglas Lu

Steven Bark

Jill Wegrzyn

Shin-Rong Hwang

Affiliations

Soon will be listed here.

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 primarily within secretory vesicles that store and secrete the mature neuropeptides to control target cellular and organ systems. This review describes interdisciplinary strategies that have elucidated two primary protease pathways for prohormone processing consisting of the cysteine protease pathway mediated by secretory vesicle cathepsin L and the well-known subtilisin-like proprotein convertase pathway that together support neuropeptide biosynthesis. Importantly, this review discusses important areas of current and future biomedical neuropeptide research with respect to biological regulation, inhibitors, structural features of proneuropeptide and protease interactions, and peptidomics combined with proteomics for systems biological approaches. Future studies that gain in-depth understanding of protease mechanisms for generating active neuropeptides will be instrumental for translational research to develop pharmacological strategies for regulation of neuropeptide functions. Pharmacological applications for neuropeptide research may provide valuable therapeutics in health and disease.

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