Prolyl carboxypeptidase and its inhibitors in metabolism
Trends in Endocrinology and Metabolism
Enzymatic inhibitors; Food intake; Hypothalamus; Prolyl carboxypeptidase; Proopiomelanocortin
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. © 2012 Elsevier Ltd.
Jeong, J., & Diano, S. (2013). Prolyl carboxypeptidase and its inhibitors in metabolism. Trends in Endocrinology and Metabolism, 24 (2). http://dx.doi.org/10.1016/j.tem.2012.11.001