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研究依维莫司在抑制mTOR和促进自噬中的作用,作为感染中潜在的宿主导向治疗靶点。

Investigating the Role of Everolimus in mTOR Inhibition and Autophagy Promotion as a Potential Host-Directed Therapeutic Target in Infection.

作者信息

Cerni Stephen, Shafer Dylan, To Kimberly, Venketaraman Vishwanath

机构信息

Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA.

Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USA.

出版信息

J Clin Med. 2019 Feb 11;8(2):232. doi: 10.3390/jcm8020232.

Abstract

Tuberculosis (TB) is a serious infectious disease caused by the pathogen (). The current therapy consists of a combination of antibiotics over the course of four months. Current treatment protocols run into problems due to the growing antibiotic resistance of and poor compliance to the multi-drug-resistant TB treatment protocol. New treatments are being investigated that target host intracellular processes that could be effective in fighting infections. Autophagy is an intracellular process that is involved in eliminating cellular debris, as well as intracellular pathogens. Mammalian target of rapamycin (mTOR) is an enzyme involved in inhibiting this pathway. Modulation of mTOR and the autophagy cellular machinery are being investigated as potential therapeutic targets for novel treatments. In this review, we discuss the background of pathogenesis, including its interaction with the innate and adaptive immune systems, the mTOR and autophagy pathways, the interaction of with these pathways, and finally, the drug everolimus, which targets these pathways and is a potential novel therapy for TB treatment.

摘要

结核病(TB)是由病原体(此处原文括号内内容缺失)引起的一种严重传染病。目前的治疗方法是在四个月的疗程中联合使用抗生素。由于该病原体对抗生素的耐药性不断增强以及对耐多药结核病治疗方案的依从性差,当前的治疗方案遇到了问题。正在研究针对宿主细胞内过程的新疗法,这些疗法可能对对抗该病原体感染有效。自噬是一种细胞内过程,参与清除细胞碎片以及细胞内病原体。雷帕霉素哺乳动物靶点(mTOR)是一种参与抑制该途径的酶。mTOR和自噬细胞机制的调节正在作为新型结核病治疗的潜在治疗靶点进行研究。在本综述中,我们讨论了结核病发病机制的背景,包括其与固有免疫和适应性免疫系统的相互作用、mTOR和自噬途径、该病原体与这些途径的相互作用,以及最后,靶向这些途径的药物依维莫司,它是一种潜在的结核病新型治疗药物。

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