On the role of prolyl oligopeptidase in health and disease

Abstract Prolyl oligopeptidase (POP) is a serine peptidase which digests small peptide-like hormones, neuroactive peptides, and various cellular factors. Therefore, this peptidase has been implicated in many physiological processes as well as in some psychiatric disorders, most probably through inte...

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Published in:Neuropeptides (Edinburgh) 2007-02, Vol.41 (1), p.1-24
Main Authors: Garcia-Horsman, JA, Maennistoe, P T, Venaelaeinen, JI
Format: Article
Language:English
Subjects:
Advanced Basic Science
Amino Acid Sequence
Animals
Arginine-vasopressin
Biological and medical sciences
Endocrinology & Metabolism
Fundamental and applied biological sciences. Psychology
Gonadoliberin
Humans
Inositol cycle
Memory and learning
Models, Molecular
Molecular Sequence Data
Neuropeptide metabolism
Neuropeptides - chemistry
Neuropeptides - pharmacology
Oligopeptides - physiology
Proline - physiology
Prolyl oligopeptidase
Protein Conformation
Reference Values
Substance P
Thyroliberin
Vertebrates: endocrinology
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Summary:Abstract Prolyl oligopeptidase (POP) is a serine peptidase which digests small peptide-like hormones, neuroactive peptides, and various cellular factors. Therefore, this peptidase has been implicated in many physiological processes as well as in some psychiatric disorders, most probably through interference in inositol cycle. Intense research has been performed to elucidate, on the one hand, the basic structure, ligand binding, and kinetic properties of POP, and on the other, the pharmacology of its inhibitors. There is fairly strong evidence of in vivo importance of POP on substance P, arginine vasopressin, thyroliberin and gonadoliberin metabolism. However, information about the biological relevance of POP is not yet conclusive. Evidence regarding the physiological role of POP is lacking, which is surprising considering that peptidase inhibitors have been exploited for drug development, some of which are currently in clinical trials as memory enhancers for the aged and in a variety of neurological disorders. Here we review the recent progress on POP research and evaluate the relevance of the peptidase in the metabolism of various neuropeptides. The recognition of novel forms and relatives of POP may improve our understanding of how this family of proteins functions in normal and in neuropathological conditions.
ISSN:0143-4179
1532-2785
DOI:10.1016/j.npep.2006.10.004