title: Prolyl carboxypeptidase and its inhibitors in metabolism.
abstract: 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.
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jin Kwon
authors.initials: JK
authors.lastname: Jeong
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diano
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011333:Pro-Opiomelanocortin; D000626:Aminopeptidases; C022450:prolyl aminopeptidase