Ligands for peripheral benzodiazepine binding sites in glial cells
Ligands for peripheral benzodiazepine binding sites in glial cells
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DOI：
10.1016/j.brainresrev.2004.12.010
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Banati, RB
中科院分区：
文献类型：
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作者：
Kassiou, M;Meikle, SR;Banati, RB
在患病大脑内，神经胶质细胞，特别是小胶质细胞，表达称为“外周苯二氮卓结合位点（PBBS）”或“外周苯二氮卓受体（PBR）”的多聚蛋白复合物。 PBBS 的表达取决于细胞的功能状态，并且在神经胶质细胞中由多种激活刺激触发。在健康的大脑中，除了脉络丛、室管膜层、血管周围细胞、中央管、脑干中的某些核团和小脑层中可能存在 PBBS 之外，PBBS 几乎不存在。同样，由于缺乏血脑屏障而含有更多活性神经胶质细胞的区域，例如垂体或第四脑室底部的后部区域，显示出一定程度的组成性表达。PBBS 的实质从头表达与激活的神经胶质细胞的存在紧密相关，而激活的神经胶质细胞通常只在受进展性疾病影响的组织中发现，这使得 PBBS 成为检测和测量活跃疾病过程的通用标记物。大脑。因此，用于正电子发射断层扫描（PET）的 PBBS 的特定放射性配体可以提供敏感的体内神经病理活动指数。虽然 PBBS 的原型配体是可用的，但未来的研究需要集中于开发新的配体，这些配体具有改进的药效学特性，并且能够区分外周苯二氮卓受体复合物的不同的、仍不充分理解的功能状态。 (c) 2004 Elsevier B.V. 保留所有权利。
Within the diseased brain, glial cells and in particular, microglia, express a multimeric protein complex termed "peripheral benzodiazepine binding sites (PBBS)" or "peripheral benzodiazepine receptor (PBR)". The expression of the PBBS is dependent on the functional state of the cell and in glial cells is triggered by a wide range of activating stimuli. In the healthy brain, the PBBS are nearly absent with the notable exception of the choroid plexus, ependymal layer, perivascular cells, central canal, possibly certain nuclei in the brainstem and layers in the cerebellum where a constitutive presence of the PBBS is found. Likewise, areas that due to the absence of the blood-brain barrier contain more active glial cells, such as the pituitary gland, or the area postrema at floor of the 4th ventricle show a degree of constitutive expression.The tight correlation of the parenchymal de novo expression of the PBBS with the presence of activated glial cells, that in turn are usually only found in tissue affected by progressive disease, establishes the PBBS as a generic marker for the detection and measurement of active disease processes in the brain. Specific radioligands of the PBBS for use in positron emission tomography (PET) may thus provide a sensitive in vivo index of neuropathological activity. Whilst prototype ligands for the PBBS are available, future research needs to focus on the development of new ligands with improved pharmacodynamic properties and the ability to discriminate between the different, still insufficiently understood functional states of the peripheral benzodiazepine receptor complex. (c) 2004 Elsevier B.V. All rights reserved.