Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Trends Mol Med. 2018 Oct;24(10):838-855. doi: 10.1016/j.molmed.2018.07.007. Epub 2018 Aug 9.
The lack of effective treatment options for chronic neurological conditions, such as multiple sclerosis (MS), highlights the need to re-evaluate disease pathophysiology in the process of identifying novel therapeutic targets. The persistent activation of mononuclear phagocytes (MPs) is one of the major drivers of neurodegeneration and it sustains central nervous system (CNS) damage. Mitochondrial metabolism influences the activity of MPs, and the metabolites that they produce have key signalling roles in inflammation. However, how changes in immune cell metabolism sustain a chronic state of neuroinflammation is not fully understood. Novel molecular and cellular therapies for chronic neuroinflammation should be developed to target mitochondrial metabolism in innate immune cells to prevent secondary neurological damage and the accumulation of irreversible disability in patients.
针对多发性硬化症（MS）等慢性神经疾病缺乏有效治疗方法的现状，凸显了在确定新的治疗靶点过程中重新评估疾病病理生理学的必要性。单核吞噬细胞（MPs）的持续激活是导致神经退行性变的主要驱动因素之一，它会持续损害中枢神经系统（CNS）。线粒体代谢会影响 MPs 的活性，而 MPs 产生的代谢物在炎症中具有关键的信号作用。然而，免疫细胞代谢的变化如何维持慢性神经炎症状态尚不完全清楚。应该开发针对固有免疫细胞中线粒体代谢的新型分子和细胞疗法，以防止继发性神经损伤和患者不可逆转残疾的积累。
