Hunting for peptide substrates of prolyl oligopeptidase: classical versus non-classical bioactive peptides

• Published in: CNS & neurological disorders drug targets Vol. 10; no. 3; p. 319
• Main Authors: Tenorio-Laranga, Jofre, Männistö, Pekka T, García-Horsman, J Arturo
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.05.2011
• Subjects: Brain - enzymology; Brain - metabolism; Drug Discovery - methods; Humans; Molecular Targeted Therapy; Neuropeptides - physiology; Serine Endopeptidases - physiology; Substrate Specificity - physiology
• ISSN: 1996-3181
• DOI: 10.2174/187152711794653841

Prolyl oligopeptidase (POP) is a serine protease that cleaves peptides shorter than 30-mer at the carboxyl side of an internal proline. POP has been proposed to be involved in some pathologies including mood disorders and neurodegenerative diseases. However, the physiological role of POP remains unknown. To validate POP as a drug target, it is essential to obtain a thorough understanding of its function in vivo. Identification of physiological substrates and products of POP is an important step towards this goal. Recent peptidomic studies have revealed some biological substrates of POP and have given information about the in vivo consequences of POP inhibition. The aim of this review is to evaluate new advances in this research area and to critically confront these data with initial conclusions and proposals. It seems that substantial activity of POP occurs intracellularly in contrast to the previously proposed role of this peptidase on the direct degradation of extracellular neuropeptides.