Department of Clinical Neurosciences and National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom.
Front Immunol. 2021 Jun 23;12:705920. doi: 10.3389/fimmu.2021.705920. eCollection 2021.
Compelling evidence exists that patients with chronic neurological conditions, which includes progressive multiple sclerosis, display pathological changes in neural metabolism and mitochondrial function. However, it is unknown if a similar degree of metabolic dysfunction occurs also in non-neural cells in the central nervous system. Specifically, it remains to be clarified (i) the full extent of metabolic changes in tissue-resident microglia and infiltrating macrophages after prolonged neuroinflammation (e.g., at the level of chronic active lesions), and (ii) whether these alterations underlie a unique pathogenic phenotype that is amenable for therapeutic targeting. Herein, we discuss how cell metabolism and mitochondrial function govern the function of chronic active microglia and macrophages brain infiltrates and identify new metabolic targets for therapeutic approaches aimed at reducing smoldering neuroinflammation.
有确凿的证据表明，患有慢性神经疾病（包括进行性多发性硬化症）的患者，其神经代谢和线粒体功能会出现病理性变化。然而，目前尚不清楚中枢神经系统中的非神经细胞是否也存在类似程度的代谢功能障碍。具体而言，仍有待阐明：（i）在长时间的神经炎症（例如慢性活动性病变）后，组织驻留的小胶质细胞和浸润的巨噬细胞中的代谢变化的全部程度；以及（ii）这些改变是否构成了一种独特的、可用于治疗靶向的致病表型。本文讨论了细胞代谢和线粒体功能如何控制慢性活动性小胶质细胞和巨噬细胞脑浸润的功能，并确定了旨在减少潜伏性神经炎症的治疗方法的新代谢靶点。
