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针对主调控因子 mTOR:一种预防寄生虫感染神经后果的新方法?

Targeting the master regulator mTOR: a new approach to prevent the neurological of consequences of parasitic infections?

机构信息

School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia.

出版信息

Parasit Vectors. 2017 Nov 21;10(1):581. doi: 10.1186/s13071-017-2528-3.

Abstract

A systematic analysis of 240 causes of death in 2013 revealed that parasitic diseases were responsible for more than one million deaths. The vast majority of these fatalities resulted from protozoan infections presenting with neurological sequelae. In the absence of a vaccine, development of effective therapies is essential to improving global public health. In 2015, an intriguing strategy to prevent cerebral malaria was proposed by Gordon et al. 2015 mBio, 6:e00625. Their study suggested that inhibition of the mammalian target of rapamycin prevented experimental cerebral malaria by blocking the damage to the blood brain barrier and stopping the accumulation of parasitized red blood cells and T cells in the brain. Here, we hypothesize that the same therapeutic strategy could be adopted for other protozoan infections with a brain tropism, to prevent cerebral parasitosis by limiting pathogen replication and preventing immune mediated destruction of brain tissue.

摘要

对 2013 年 240 例死因的系统分析显示,寄生虫病导致的死亡人数超过 100 万。这些死亡病例绝大多数是由原生动物感染引起的神经系统后遗症导致的。在没有疫苗的情况下,开发有效的治疗方法对于改善全球公共卫生至关重要。2015 年,Gordon 等人提出了一种预防脑疟疾的有趣策略。2015 年 mBio,6:e00625。他们的研究表明,通过阻止血脑屏障的损伤和阻止寄生红细胞和 T 细胞在大脑中的积累,抑制哺乳动物雷帕霉素靶蛋白可阻止实验性脑疟疾。在这里,我们假设相同的治疗策略可以用于其他具有脑部趋向性的原生动物感染,通过限制病原体复制和防止免疫介导的脑组织破坏来预防脑寄生虫病。

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本文引用的文献

1
A quantitative brain map of experimental cerebral malaria pathology.实验性脑型疟疾病理学的定量脑图谱。
PLoS Pathog. 2017 Mar 8;13(3):e1006267. doi: 10.1371/journal.ppat.1006267. eCollection 2017 Mar.
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Regulation of innate immune cell function by mTOR.mTOR对天然免疫细胞功能的调节
Nat Rev Immunol. 2015 Oct;15(10):599-614. doi: 10.1038/nri3901.
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Pathogenic CD8+ T cells in experimental cerebral malaria.实验性脑型疟疾中的致病 CD8+ T 细胞。
Semin Immunopathol. 2015 May;37(3):221-31. doi: 10.1007/s00281-015-0476-6. Epub 2015 Mar 13.
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mTOR and metabolic regulation of conventional and regulatory T cells.mTOR与传统T细胞和调节性T细胞的代谢调控
J Leukoc Biol. 2015 May;97(5):837-847. doi: 10.1189/jlb.2RI0814-408R. Epub 2015 Feb 24.

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