The 18 kDa translocator protein, microglia and neuroinflammation.
The 18 kDa translocator protein, microglia and neuroinflammation.
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DOI：
10.1111/bpa.12196
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Banati RB
中科院分区：
文献类型：
--
作者：
Liu GJ;Middleton RJ;Hatty CR;Kam WW;Chan R;Pham T;Harrison-Brown M;Dodson E;Veale K;Banati RB
18 kDa转运蛋白（TSPO），以前称为外周苯二氮卓受体，在受损的大脑中表达。它已被称为“神经炎症”的成像标记物，指示活动性疾病，最好解释为非诊断性生物标志物和疾病分期工具，指的是组织病理学而不是疾病病因学。TSPO作为药物靶标的治疗潜力主要基于以下理解：它是胆固醇易位所需的线粒体外膜蛋白，从而调节类固醇合成的速率。这一关键作用以及TSPO的进化保守性支持了这样一种信念，即TSPO的任何缺失或突变都应与显著的生理缺陷相关，或者与生命完全不相容。然而，与预测相反，完全Tspo敲除小鼠是可行的，并且在其寿命期间不显示如果胆固醇转运和类固醇合成显著受损所预期的表型。因此，TSPO的“易位”功能仍有待进一步证实。在这里，我们讨论了文献之前和之后的新命名TSPO介绍和审查一些新的发现。鉴于围绕TSPO功能的争议，我们强调识别具有确认选择性的化合物的持续重要性，并建议在特定疾病背景下分析TSPO表达，而不仅仅是等同于“神经炎症”的具体概念。
The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is expressed in the injured brain. It has become known as an imaging marker of “neuroinflammation” indicating active disease, and is best interpreted as a nondiagnostic biomarker and disease staging tool that refers to histopathology rather than disease etiology. The therapeutic potential of TSPO as a drug target is mostly based on the understanding that it is an outer mitochondrial membrane protein required for the translocation of cholesterol, which thus regulates the rate of steroid synthesis. This pivotal role together with the evolutionary conservation of TSPO has underpinned the belief that any loss or mutation of TSPO should be associated with significant physiological deficits or be outright incompatible with life. However, against prediction, full Tspo knockout mice are viable and across their lifespan do not show the phenotype expected if cholesterol transport and steroid synthesis were significantly impaired. Thus, the “translocation” function of TSPO remains to be better substantiated. Here, we discuss the literature before and after the introduction of the new nomenclature for TSPO and review some of the newer findings. In light of the controversy surrounding the function of TSPO, we emphasize the continued importance of identifying compounds with confirmed selectivity and suggest that TSPO expression is analyzed within specific disease contexts rather than merely equated with the reified concept of “neuroinflammation.”
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影响因子：
4.1
作者：
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通讯作者：
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影响因子：
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DOI：
10.1016/j.bbagrm.2011.09.001
发表时间：
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作者：
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影响因子：
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作者：
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通讯作者：
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