Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system

NEUROBIOLOGY OF DISEASE

卷:152

Review

Yang, Sheng¹  Qin, Chuan¹  Hu, Zi-Wei¹  Zhou, Luo-Qi¹  Yu, Hai-Han¹  Chen, Man¹  Bosco, Dale B.²  Wang, Wei¹  Wu, Long-Jun²  Tian, Dai-Shi¹ 

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Neurol, Wuhan 430030, Peoples R China

[2] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA

关键词: Microglia;    Inflammation;    Metabolism;    Reprogramming;    Glycolysis;    Oxidative phosphorylation;   

DOI  :  10.1016/j.nbd.2021.105290

来源: Elsevier

【 摘 要 】

In response to various types of environmental and cellular stress, microglia rapidly activate and exhibit either pro-or anti-inflammatory phenotypes to maintain tissue homeostasis. Activation of microglia can result in changes in morphology, phagocytosis capacity, and secretion of cytokines. Furthermore, microglial activation also induces changes to cellular energy demand, which is dependent on the metabolism of various metabolic substrates including glucose, fatty acids, and amino acids. Accumulating evidence demonstrates metabolic reprogramming acts as a key driver of microglial immune response. For instance, microglia in pro-inflammatory states preferentially use glycolysis for energy production, whereas, cells in anti-inflammatory states are mainly powered by oxidative phosphorylation and fatty acid oxidation. In this review, we summarize recent findings regarding microglial metabolic pathways under physiological and pathological circumtances. We will then discuss how metabolic reprogramming can orchestrate microglial response to a variety of central nervous system pathologies. Finally, we highlight how manipulating metabolic pathways can reprogram microglia towards beneficial functions, and illustrate the therapeutic potential for inflammation-related neurological diseases.