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针对系统性红斑狼疮代谢途径的潜在治疗方法。

Potential therapies targeting metabolic pathways in systemic lupus erythematosus.

机构信息

Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan.

出版信息

Clin Immunol. 2024 Jun;263:110224. doi: 10.1016/j.clim.2024.110224. Epub 2024 Apr 20.

Abstract

The pathophysiology of systemic lupus erythematosus (SLE) is multifactorial and involves alterations in metabolic pathways, including glycolysis, lipid metabolism, amino acid metabolism, and mitochondrial dysfunction. Increased glycolysis in SLE T cells, which is associated with elevated glucose transporter 1 expression, suggests targeting glucose transporters and hexokinase as potential treatments. Abnormalities in lipid metabolism, particularly in lipid rafts and enzymes, present new therapeutic targets. This review discusses how changes in glutaminolysis and tryptophan metabolism affect T-cell function, suggesting new therapeutic interventions, as well as mitochondrial dysfunction in SLE, which increases reactive oxygen species. The review also emphasizes that modulating metabolic pathways in immune cells is a promising approach for SLE treatment, and can facilitate personalized therapies based on individual metabolic profiles of patients with SLE. The review provides novel insights into strategies for managing SLE.

摘要

系统性红斑狼疮 (SLE) 的病理生理学是多因素的,涉及代谢途径的改变,包括糖酵解、脂质代谢、氨基酸代谢和线粒体功能障碍。SLE T 细胞中的糖酵解增加,与葡萄糖转运蛋白 1 表达升高有关,这表明靶向葡萄糖转运蛋白和己糖激酶可能是潜在的治疗方法。脂质代谢异常,特别是在脂筏和酶中,呈现出新的治疗靶点。这篇综述讨论了谷氨酰胺分解和色氨酸代谢的变化如何影响 T 细胞功能,提示了新的治疗干预措施,以及 SLE 中的线粒体功能障碍增加了活性氧。该综述还强调,调节免疫细胞中的代谢途径是治疗 SLE 的一种有前途的方法,并可以根据 SLE 患者的个体代谢特征促进个性化治疗。该综述为 SLE 的管理策略提供了新的见解。

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