Microglia metabolism in health and disease
Microglia metabolism in health and disease
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DOI：
10.1016/j.neuint.2018.11.006
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发表时间：
2019-11-01
影响因子：
4.2
通讯作者：
Prinz, Marco
中科院分区：
文献类型：
--
作者：
Borst, Katharina;Schwabenland, Marius;Prinz, Marco
在过去的十年中，在了解免疫系统如何对侮辱做出反应方面取得了巨大进展。在这一过程中，很明显，这些免疫反应受到严格的调节，并与免疫细胞中不同的代谢变化交联。人们主要对T细胞亚型进行了广泛的研究，它们在分化过程和激活状态期间使用不同的代谢途径。此外，后来还确定，骨髓细胞的先天免疫细胞谱系包括各种不同的骨髓源性巨噬细胞亚群以及组织特异性巨噬细胞，其引起比简单杀死细菌更多的功能。为了执行这种多种多样的功能，巨噬细胞也使用不同的代谢途径，并受到关键代谢调节剂的严格调节，例如雷帕霉素（mTOR）的机制靶标。在活化后，细胞内发生代谢变化以满足表型转换的要求。此外，代谢变化与先天免疫细胞显示适应性免疫应答标志的能力相关。关于骨髓细胞和特别是小胶质细胞在体内的特定代谢变化知之甚少。小胶质细胞是神经退行性疾病和神经炎性疾病的关键参与者，并已成为医学研究的主要目标。在这里，我们回顾了小胶质细胞代谢和小胶质细胞表型与神经炎症和神经退行性疾病的连接的现有数据。最后，我们将讨论我们关于细胞代谢的知识如何用于开发神经系统疾病的新治疗方案。
In the last decade tremendous progress has been made in understanding how the immune system reacts to insults. During this progress it became obvious that those immune responses are tightly regulated and cross-linked with distinct metabolic changes in immune cells. Extensive research has been conducted mainly on subtypes of T cells, which use different metabolic pathways during differentiation processes and activation states. In addition, it has also been established later, that the innate immune cell lineage of myeloid cells includes a variety of different subsets of bone marrow-derived as well as tissue-specific macrophages, which elicit much more functions than simply killing bacteria. To execute this high variety of functions, also macrophages use different metabolic pathways and are tightly regulated by key metabolic regulators, such as the mechanistic target of rapamycin (mTOR). Upon activation, metabolic changes within the cell occur to meet the requirements of the phenotypic switch. In addition, metabolic changes correlate with the ability of innate immune cells to show hallmarks of adaptive immune responses.Little is known about specific metabolic changes of myeloid cells and specifically microglia in vivo. Microglia are key players in neurodegenerative and neuroinflammatory diseases and have become a major target of medical research. Here, we review the existing data on microglia metabolism and the connection of microglia phenotypes with neuroinflammatory and neurodegenerative diseases. Lastly, we will discuss how our knowledge about the cellular metabolism might be used to develop new treatment options for neurological diseases.