Title:Is there Any Correlation Between Binding and Functional Effects at the Translocator Protein (TSPO) (18 kDa)?
VOLUME: 12 ISSUE: 4
Author(s):A. M. Scarf, K. M. Auman and M. Kassiou
Affiliation:Drug Discovery Laboratory, Brain and Mind Research Institute, University of Sydney NSW 2050, Australia.
Keywords:Apoptosis, multiple binding sites, neuroprotection, radioligand binding, steroidogenesis, translocator
protein (TSPO)
Abstract:The translocator protein (TSPO) is a potential drug target for the treatment of CNS diseases, with
TSPO ligands being able to modulate steroidogenesis, apoptosis, and cell proliferation. While there exist
multiple TSPO binding sites, the nature of these sites – either overlapping or allosterically linked – remains
largely uncharacterized. Furthermore, while evidence suggests that microglial activation and polymerization
result in changes to TSPO binding sites, these changes are poorly understood. While current pharmacophoric
models can be used to synthesize TSPO ligands with high affinity and selectivity, these models are unable to
predict ligands with desirable functional effects. Better characterization of TSPO binding sites in health and
disease may provide insight into particular sites which mediate promising therapeutic profiles, thus refining the
TSPO pharmacophore.
