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Is there Any Correlation Between Binding and Functional Effects at the Translocator Protein (TSPO) (18 kDa)?

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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.
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  • Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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