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中枢神经系统疾病进展和缓解中的脂肪酸代谢。

Fatty acid metabolism in the progression and resolution of CNS disorders.

机构信息

Deparment of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan Building C, Diepenbeek, Belgium.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan, 1117, Amsterdam, The Netherlands.

出版信息

Adv Drug Deliv Rev. 2020;159:198-213. doi: 10.1016/j.addr.2020.01.004. Epub 2020 Jan 25.

Abstract

Recent advances in lipidomics and metabolomics have unveiled the complexity of fatty acid metabolism and the fatty acid lipidome in health and disease. A growing body of evidence indicates that imbalances in the metabolism and level of fatty acids drive the initiation and progression of central nervous system (CNS) disorders such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. Here, we provide an in-depth overview on the impact of the β-oxidation, synthesis, desaturation, elongation, and peroxidation of fatty acids on the pathophysiology of these and other neurological disorders. Furthermore, we discuss the impact of individual fatty acids species, acquired through the diet or endogenously synthesized in mammals, on neuroinflammation, neurodegeneration, and CNS repair. The findings discussed in this review highlight the therapeutic potential of modulators of fatty acid metabolism and the fatty acid lipidome in CNS disorders, and underscore the diagnostic value of lipidome signatures in these diseases.

摘要

脂质组学和代谢组学的最新进展揭示了脂肪酸代谢和脂肪酸脂质组在健康和疾病中的复杂性。越来越多的证据表明,脂肪酸代谢和水平的失衡会导致中枢神经系统(CNS)疾病的发生和发展,如多发性硬化症、阿尔茨海默病和帕金森病。在这里,我们深入概述了脂肪酸的β-氧化、合成、去饱和、延长和过氧化对这些和其他神经疾病的病理生理学的影响。此外,我们还讨论了通过饮食获得或哺乳动物内源性合成的单个脂肪酸种类对神经炎症、神经退行性变和中枢神经系统修复的影响。本文综述讨论的结果强调了脂肪酸代谢和脂肪酸脂质组调节剂在中枢神经系统疾病中的治疗潜力,并突出了脂质组谱在这些疾病中的诊断价值。

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