Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV.
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV.
J Neurosci Res. 2018 Jun;96(6):978-988. doi: 10.1002/jnr.24212. Epub 2018 Jan 6.
The brain is the most metabolically active organ in the body. This high metabolic demand is apparent in that 60% of the brain is comprised of mitochondria-enriched cells. A disruption of the brain's ability to meet this immense metabolic demand is central to the pathogenesis of a multitude of neurological disorders, which range from depression to Alzheimer's disease. Central to these pathologies are glial signaling and energy metabolism cascades regulating apoptosis and inflammation. Thus, diseases causing inflammation and disruption of metabolism can be correlated with glial reactivity. Acutely, reactive gliosis provides a mechanism for limiting the progression of a disease. Following chronic activation, the ability of reactive gliosis to limit disease progression decreases and, in some cases, transitions into a harmful state. The necessity for a noninvasive biomarker of disease in the brain has linked reactive gliosis with an upregulation of translocator protein (TSPO). TSPO is an 18kDa protein that is both a therapeutic target for multiple acute and chronic neuroinflammatory diseases and the leading biomarker for Alzheimer's disease. Although a central function of TSPO is not well known, the protein was named for its ability to translocate cholesterol. Increased TSPO expression is an indicator of disrupted metabolic activity and increased reactive oxygen production. The changes in TSPO expression levels both temporally and spatially relate to the pathogenesis of stroke, Alzheimer's disease, traumatic brain injury, and depression. Therefore, research into the basic function and potential therapeutics targeting TSPO will have broad implications for many diseases of the brain.
大脑是人体中代谢最活跃的器官。这种高代谢需求在大脑中 60%的组成部分是富含线粒体的细胞中表现得尤为明显。大脑无法满足这种巨大代谢需求的能力的破坏是多种神经疾病发病机制的核心，这些疾病的范围从抑郁症到阿尔茨海默病。胶质细胞信号和能量代谢级联调节细胞凋亡和炎症是这些病理学的核心。因此，导致炎症和代谢紊乱的疾病可以与神经胶质细胞的反应性相关联。急性反应性神经胶质增生为限制疾病进展提供了一种机制。在慢性激活后，反应性神经胶质增生限制疾病进展的能力下降，在某些情况下，会过渡到有害状态。由于需要在大脑中找到一种非侵入性的疾病生物标志物，因此将反应性神经胶质增生与转位蛋白（TSPO）的上调联系起来。TSPO 是一种 18kDa 的蛋白质，既是多种急性和慢性神经炎症性疾病的治疗靶点，也是阿尔茨海默病的主要生物标志物。尽管 TSPO 的核心功能尚不清楚，但该蛋白因其转运胆固醇的能力而得名。TSPO 表达增加是代谢活动紊乱和活性氧产生增加的指标。TSPO 表达水平的变化在时间和空间上都与中风、阿尔茨海默病、创伤性脑损伤和抑郁症的发病机制有关。因此，针对 TSPO 的基本功能和潜在治疗方法的研究将对大脑的许多疾病产生广泛的影响。
