Runtsch Marah C, Ferrara Giovanni, Angiari Stefano
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
J Neurochem. 2021 Jul;158(1):36-58. doi: 10.1111/jnc.15169. Epub 2020 Sep 22.
Neuroinflammatory and neurodegenerative diseases are characterized by the recruitment of circulating blood-borne innate and adaptive immune cells into the central nervous system (CNS). These leukocytes sustain the detrimental response in the CNS by releasing pro-inflammatory mediators that induce activation of local glial cells, blood-brain barrier (BBB) dysfunction, and neural cell death. However, infiltrating peripheral immune cells could also dampen CNS inflammation and support tissue repair. Recent advances in the field of immunometabolism demonstrate the importance of metabolic reprogramming for the activation and functionality of such innate and adaptive immune cell populations. In particular, an increasing body of evidence suggests that the activity of metabolites and metabolic enzymes could influence the pathogenic potential of immune cells during neuroinflammatory and neurodegenerative disorders. In this review, we discuss the role of intracellular metabolic cues in regulating leukocyte-mediated CNS damage in Alzheimer's and Parkinson's disease, multiple sclerosis and stroke, highlighting the therapeutic potential of drugs targeting metabolic pathways for the treatment of neurological diseases.
神经炎症性疾病和神经退行性疾病的特征是循环血源性先天性和适应性免疫细胞募集进入中枢神经系统（CNS）。这些白细胞通过释放促炎介质维持中枢神经系统中的有害反应，这些介质会诱导局部胶质细胞激活、血脑屏障（BBB）功能障碍和神经细胞死亡。然而，浸润的外周免疫细胞也可以减轻中枢神经系统炎症并支持组织修复。免疫代谢领域的最新进展表明，代谢重编程对于此类先天性和适应性免疫细胞群体的激活和功能至关重要。特别是，越来越多的证据表明，代谢物和代谢酶的活性可能会影响神经炎症性和神经退行性疾病期间免疫细胞的致病潜力。在这篇综述中，我们讨论了细胞内代谢线索在调节阿尔茨海默病、帕金森病、多发性硬化症和中风中白细胞介导的中枢神经系统损伤中的作用，强调了靶向代谢途径的药物治疗神经疾病的潜力。
