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.
Keywords: Apoptosis, multiple binding sites, neuroprotection, radioligand binding, steroidogenesis, translocator protein (TSPO)
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