Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, 300 Prince Phillip Dr. St. John's, St. John's, NL, A1B 3V6, Canada.
J Neuroinflammation. 2024 Nov 17;21(1):300. doi: 10.1186/s12974-024-03296-0.
Microglia, the resident immune cells of the central nervous system, emerge in the brain during early embryonic development and persist throughout life. They play essential roles in brain homeostasis, and their dysfunction contributes to neuroinflammation and the progression of neurodegenerative diseases. Recent studies have uncovered an intricate relationship between microglia functions and metabolic processes, offering fresh perspectives on disease mechanisms and possible treatments. Despite these advancements, there are still significant gaps in our understanding of how metabolic dysregulation affects microglial phenotypes in these disorders. This review aims to address these gaps, laying the groundwork for future research on the topic. We specifically examine how metabolic shifts in microglia, such as the transition from oxidative phosphorylation and mitochondrial metabolism to heightened glycolysis during proinflammatory states, impact the disease progression in Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Additionally, we explore the role of iron, fatty and amino acid metabolism in microglial homeostasis and repair. Identifying both distinct and shared metabolic adaptations in microglia across neurodegenerative diseases could reveal common therapeutic targets and provide a deeper understanding of disease-specific mechanisms underlying multiple CNS disorders.
小胶质细胞是中枢神经系统的固有免疫细胞,在胚胎早期发育过程中出现,并在整个生命过程中持续存在。它们在脑内稳态中发挥着重要作用,其功能障碍导致神经炎症和神经退行性疾病的进展。最近的研究揭示了小胶质细胞功能与代谢过程之间的复杂关系,为疾病机制和可能的治疗方法提供了新的视角。尽管取得了这些进展,但我们对代谢失调如何影响这些疾病中小胶质细胞表型的理解仍然存在很大的差距。本综述旨在填补这些空白,为该主题的未来研究奠定基础。我们特别研究了小胶质细胞中的代谢转变,例如在促炎状态下从氧化磷酸化和线粒体代谢向糖酵解的转变,如何影响阿尔茨海默病、多发性硬化症、帕金森病、肌萎缩侧索硬化症和亨廷顿病的疾病进展。此外,我们还探讨了铁、脂肪酸和氨基酸代谢在小胶质细胞稳态和修复中的作用。在神经退行性疾病中小胶质细胞中识别出独特和共同的代谢适应性,可以揭示共同的治疗靶点,并深入了解多种中枢神经系统疾病的特定机制。