Neuropharmacology

Biography

Biography: Salvatore Guccione

Abstract

G-Protein Coupled Receptors (GPCRs) are major contributors to the information flow into cells and, as such, are involved in a wide range of physiological processes and diseases, including those affecting the cardiovascular, nervous, endocrine, and immune systems. Therefore, GPCRs are potential druggable targets (60-70%) in a multitude of therapeutics areas. Moreover, GPCRs represent more than one third of the targets for currently marketed drugs. The structures of GPCRs needs to be elucidated in order to employ them in drug design and discovery, using the methods of “Structure Based Drug Design” (SBDD). Direct experimental study of GPCR structures is currently difficult because of the native membrane environment, which poses limitations to the purification and crystallization process. High resolution structural information is available only for ~2% of the GPCRs. Based on statistical analysis of (Y)/Phi (F) and RMSDs (Root Mean Square Deviation) of the trans-membrane domains, some tips are presented to make easier modelling GPCRs finally getting reliable models. Serotonergic system modulation may present a promising strategy for slowing AD progression and improving cognition. Increasing serotonin (5-HT) signaling and developing molecules that enhance 5-HT concentration in the synaptic cleft have been debated as possible therapeutic strategies to slow the progression of Alzheimer’s disease. A model of a membrane bound G-protein system to study all the mechanisms involved in the 5-HT7 activation will be presented. These findings could be exploited to rationally design new ligands to selectively regulate different transduction pathways underlying a number of different disorders.