Discipline of Pharmacology, University of Sydney NSW 2006, Australia.
Curr Mol Med. 2012 May;12(4):387-97. doi: 10.2174/1566524011207040387.
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.
转位蛋白（TSPO）是治疗中枢神经系统疾病的潜在药物靶点，TSPO 配体能够调节类固醇生成、细胞凋亡和细胞增殖。虽然存在多个 TSPO 结合位点，但这些位点的性质（重叠或变构连接）在很大程度上仍未得到充分描述。此外，尽管有证据表明小胶质细胞的激活和聚合导致 TSPO 结合位点发生变化，但这些变化仍知之甚少。虽然当前的药效团模型可用于合成具有高亲和力和选择性的 TSPO 配体，但这些模型无法预测具有理想功能效果的配体。更好地描述健康和疾病状态下的 TSPO 结合位点可能有助于深入了解介导有前景的治疗特征的特定位点，从而完善 TSPO 药效团。
