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Trends Endocrinol Metab. 2013 Feb;24(2):61-7. doi: 10.1016/j.tem.2012.11.001. Epub 2012 Dec 12.

Prolyl carboxypeptidase and its inhibitors in metabolism.

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  • 1Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA.


Proopiomelanocortin (POMC)-expressing neurons in the hypothalamus integrate a variety of central and peripheral metabolic inputs, and regulate energy homeostasis by controlling energy expenditure and food intake. To accomplish this, a precise balance of production and degradation of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide and product of the POMC gene, in the hypothalamus, is crucial. Prolyl carboxypeptidase (PRCP) is a key enzyme that degrades α-MSH to an inactive form unable to inhibit food intake. Because it represents a new therapeutic target for the treatment of metabolic disorders, such as obesity and diabetes, efforts have been made to generate potent, brain-penetrant PRCP inhibitors. Here, we discuss the role of PRCP on energy metabolism and the development of PRCP inhibitors.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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