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TSPO 研究在神经退行性疾病、精神障碍、酒精使用障碍、创伤性脑损伤和中风中的诊断和治疗潜力:更新。

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update.

机构信息

Department of Experimental Biochemistry, Institute of Biology, Faculty of Natural Sciences and Mathematics, University Ss Cyril and Methodius, Arhimedova 3, P.O. Box 162, 1000 Skopje, Republic of North Macedonia.

Technion-Israel Institute of Technology, Faculty of Medicine, Rappaport Institute of Medical Research, 1 Efron Street, P.O. Box 9697, Haifa 31096, Israel.

出版信息

Cells. 2020 Apr 2;9(4):870. doi: 10.3390/cells9040870.

Abstract

Neuroinflammation and cell death are among the common symptoms of many central nervous system diseases and injuries. Neuroinflammation and programmed cell death of the various cell types in the brain appear to be part of these disorders, and characteristic for each cell type, including neurons and glia cells. Concerning the effects of 18-kDa translocator protein (TSPO) on glial activation, as well as being associated with neuronal cell death, as a response mechanism to oxidative stress, the changes of its expression assayed with the aid of TSPO-specific positron emission tomography (PET) tracers' uptake could also offer evidence for following the pathogenesis of these disorders. This could potentially increase the number of diagnostic tests to accurately establish the stadium and development of the disease in question. Nonetheless, the differences in results regarding TSPO PET signals of first and second generations of tracers measured in patients with neurological disorders versus healthy controls indicate that we still have to understand more regarding TSPO characteristics. Expanding on investigations regarding the neuroprotective and healing effects of TSPO ligands could also contribute to a better understanding of the therapeutic potential of TSPO activity for brain damage due to brain injury and disease. Studies so far have directed attention to the effects on neurons and glia, and processes, such as death, inflammation, and regeneration. It is definitely worthwhile to drive such studies forward. From recent research it also appears that TSPO ligands, such as PK11195, Etifoxine, Emapunil, and 2-Cl-MGV-1, demonstrate the potential of targeting TSPO for treatments of brain diseases and disorders.

摘要

神经炎症和细胞死亡是许多中枢神经系统疾病和损伤的常见症状。脑内各种细胞类型的神经炎症和程序性细胞死亡似乎是这些疾病的一部分,并且是每种细胞类型的特征,包括神经元和神经胶质细胞。关于 18kDa 转位蛋白(TSPO)对神经胶质细胞激活的影响,以及作为对氧化应激的反应机制与神经元细胞死亡相关,其表达的变化可以通过 TSPO 特异性正电子发射断层扫描(PET)示踪剂摄取来检测,这也为研究这些疾病的发病机制提供了证据。这有可能增加诊断测试的数量,以准确确定所关注疾病的阶段和发展。尽管如此,在患有神经紊乱的患者与健康对照组之间测量的第一代和第二代示踪剂的 TSPO PET 信号的结果存在差异,这表明我们仍然需要更多地了解 TSPO 的特征。对 TSPO 配体的神经保护和修复作用的研究也有助于更好地理解 TSPO 活性对脑损伤的治疗潜力,脑损伤和疾病会导致脑损伤。迄今为止的研究已经将注意力集中在神经元和神经胶质以及死亡、炎症和再生等过程的影响上。进一步推动这些研究绝对是值得的。最近的研究还表明,TSPO 配体,如 PK11195、Etifoxine、Emapunil 和 2-Cl-MGV-1,具有针对 TSPO 的靶向治疗脑疾病和紊乱的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3061/7226777/e76895f67dc0/cells-09-00870-g001.jpg

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