Computational Studies on Translocator Protein (TSPO) and its Ligands

Gabriella      Ortore; Tiziano      Tuccinardi; Adriano      Martinelli

Abstract

The Translocator Protein (18 kDa) (TSPO), previously known as the peripheral benzodiazepine receptor, is widely expressed in glial cells and in peripheral tissues and is involved in a variety of biological processes: steroidogenesis, cell growth and differentiation, apoptosis induction, etc. TSPO basal expression is up-regulated in a number of human pathologies, including a variety of tumors and neuropathologies, such as gliomas and neurodegenerative disorders (Huntingtons and Alzheimers diseases), as well as in various forms of brain injury and inflammation. Furthermore, changes in TSPO receptor levels have been found in anxiety and mood disorders. Nowadays, considerable efforts have been focused on the identification of new TSPO ligands characterized by high-affinity and selectivity. In this review, we report and analyze the main experimental data and the computational procedures and validation methods used for the construction of the TSPO receptor and ligand-based models, describing in detail the most successful results and the new trends.

Keywords: 18 kDa translocator protein (TSPO), 3D-QSAR, computational chemistry, homology model, mutagenesis data, peripheral-type benzodiazepine receptor, pharmacophoric model, virtual screening, glial cells, gliomas, neurodegenerative disorders, high-affinity and selectivity, ligand-based models