Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma.
Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma.
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DOI：
10.1016/j.expneurol.2009.04.016
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Lecanu, Laurent
中科院分区：
文献类型：
--
作者：
Papadopoulos, Vassilios;Lecanu, Laurent
关键词：
创伤性脑损伤 (TBI) 会导致身体、认知和心理缺陷，影响数百万患者。 TBI 激活多种细胞机制和分子级联反应，产生有害结果，包括神经元死亡和功能丧失。线粒体是 TBI 的主要靶标之一，表现为激活和增殖的小胶质细胞中线粒体活性增加（由于高能量需求和/或钙超载）以及活性氧增加、线粒体通透性转变变化、细胞色素 c 释放、半胱天冬酶激活、ATP 水平降低和神经元细胞死亡。易位蛋白 (TSPO) 是一种 18 kDa 线粒体外膜蛋白，与线粒体通透性转换孔相互作用，并以高亲和力与胆固醇和各类药物配体结合，包括一些苯二氮卓类药物，例如 4'-氯地西泮 (Ro5-4864)。尽管大脑中的 TSPO 水平较低，但在脑损伤和炎症后，TSPO 水平会升高。这一发现促使人们提议使用 TSPO 表达作为脑损伤和修复的标志物。 TSPO 药物配体已被证明参与线粒体呼吸和功能、线粒体类固醇和神经类固醇形成以及细胞凋亡的控制。这篇综述和评论将概述我们目前对靶向 TSPO 治疗 TBI 的益处以及 TSPO 药物配体在神经创伤中神经保护作用的机制的了解。
Traumatic brain injury (TBI) induces physical, cognitive, and psychosocial deficits that affect millions of patients. TBI activates numerous cellular mechanisms and molecular cascades that produce detrimental outcomes, including neuronal death and loss of function. The mitochondrion is one of the major targets of TBI, as seen by increased mitochondrial activity in activated and proliferating microglia (due to high energy requirements and/or calcium overload) as well as increased reactive oxygen species, changes in mitochondrial permeability transition, release of cytochrome c, caspase activation, reduced ATP levels, and cell death in neurons. Translocator protein (TSPO) is an 18-kDa outer mitochondrial membrane protein that interacts with the mitochondria permeability transition pore and binds with high affinity to cholesterol and various classes of drug ligands, including some benzodiazepines such as 4′-chlorodiazepam (Ro5-4864). Although TSPO levels in the brain are low, they are increased after brain injury and inflammation. This finding has led to the proposed use of TSPO expression as a marker of brain injury and repair. TSPO drug ligands have been shown to participate in the control of mitochondrial respiration and function, mitochondrial steroid and neurosteroid formation, as well as apoptosis. This review and commentary will outline our current knowledge of the benefits of targeting TSPO for TBI treatment and the mechanisms underlying the neuroprotective effects of TSPO drug ligands in neurotrauma.
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影响因子：
5.8
作者：
BEAUMONT, K;SKOWRONSKI, R;FANESTIL, DD
通讯作者：
FANESTIL, DD
影响因子：
4.1
作者：
Jagannathan, Pavan;Jagannathan, Jay
通讯作者：
Jagannathan, Jay
影响因子：
4.2
作者：
Hong, Seok H.;Choi, Hyun B.;McLarnon, James G.
通讯作者：
McLarnon, James G.
影响因子：
4
作者：
Azarashvili, Tamara;Grachev, Dmitry;Reiser, Georg
通讯作者：
Reiser, Georg
影响因子：
5.3
作者：
He, J;Evans, CO;Stein, DG
通讯作者：
Stein, DG