Neuropeptide Y receptors: ligand binding and trafficking suggest novel approaches in drug development

• Published in: Journal of peptide science 2011-04, Vol.17 (4), p.233-246
• Main Authors: Walther, Cornelia, Mörl, Karin, Beck-Sickinger, Annette G.
• Format: Article
• Language: English
• Subjects: Drug Design; drug development; GPCR; Humans; internalization; Ligands; Molecular Structure; Neoplasms - drug therapy; Neuropeptide Y - genetics; Neuropeptide Y - metabolism; NPY; Obesity - drug therapy; Pancreatic Polypeptide - genetics; Pancreatic Polypeptide - metabolism; Peptide YY - genetics; Peptide YY - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; receptor trafficking; Receptors, Neuropeptide Y - genetics; Receptors, Neuropeptide Y - metabolism; structure-activity relationship
• ISSN: 1075-2617; 1099-1387; 1099-1387
• DOI: 10.1002/psc.1357

NPY, PYY and PP constitute the so‐called NPY hormone family, which exert its biological functions in humans through YRs (Y1, Y2, Y4 and Y5). Systematic modulation of YR function became important as this multireceptor/multiligand system is known to mediate various essential physiological key functions and is involved in a variety of major human diseases such as epilepsy, obesity and cancer. As several YRs have been found to be overexpressed on different types of malignant tumors they emerge as promising target in modern drug development. Here, we summarize the current understanding of YRs function and the molecular mechanisms of ligand binding and trafficking. We further address recent advances in YR‐based drug design, the development of promising future drug candidates and novel approaches in YR‐targeted tumor diagnostics and therapy opportunities. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. The members of the NPY hormone family have been shown to exhibit critical effects in the regulation of many important physiological functions by acting through YRs. Therefore the NPY system emerged as one of the main targets in modern drug development. Recent advances in understanding YR functionality and YR‐targeted diagnostics and therapy are reviewed.