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靶向免疫代谢作为一种抗炎策略。

Targeting immunometabolism as an anti-inflammatory strategy.

机构信息

School of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.

出版信息

Cell Res. 2020 Apr;30(4):300-314. doi: 10.1038/s41422-020-0291-z. Epub 2020 Mar 4.

Abstract

The growing field of immunometabolism has taught us how metabolic cellular reactions and processes not only provide a means to generate ATP and biosynthetic precursors, but are also a way of controlling immunity and inflammation. Metabolic reprogramming of immune cells is essential for both inflammatory as well as anti-inflammatory responses. Four anti-inflammatory therapies, DMF, Metformin, Methotrexate and Rapamycin all work by affecting metabolism and/or regulating or mimicking endogenous metabolites with anti-inflammatory effects. Evidence is emerging for the targeting of specific metabolic events as a strategy to limit inflammation in different contexts. Here we discuss these recent developments and speculate on the prospect of targeting immunometabolism in the effort to develop novel anti-inflammatory therapeutics. As accumulating evidence for roles of an intricate and elaborate network of metabolic processes, including lipid, amino acid and nucleotide metabolism provides key focal points for developing new therapies, we here turn our attention to glycolysis and the TCA cycle to provide examples of how metabolic intermediates and enzymes can provide potential novel therapeutic targets.

摘要

免疫代谢领域的研究进展告诉我们,细胞代谢反应和过程不仅为产生 ATP 和生物合成前体提供了一种途径,而且还可以控制免疫和炎症反应。免疫细胞的代谢重编程对于炎症和抗炎反应都是必不可少的。四种抗炎疗法,即 DMF、二甲双胍、甲氨蝶呤和雷帕霉素,都通过影响代谢和/或调节或模拟具有抗炎作用的内源性代谢物来发挥作用。越来越多的证据表明,针对特定代谢事件作为一种策略,可以限制不同情况下的炎症。在这里,我们讨论这些最新的进展,并推测靶向免疫代谢的前景,以开发新的抗炎治疗方法。随着越来越多的证据表明,包括脂质、氨基酸和核苷酸代谢在内的复杂而精细的代谢过程网络发挥着作用,为开发新的治疗方法提供了关键的焦点,我们现在将注意力转向糖酵解和三羧酸 (TCA) 循环,以提供代谢中间产物和酶如何为潜在的新治疗靶点提供示例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7797/7118080/a390a65667ea/41422_2020_291_Fig1_HTML.jpg

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