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DOI | 10.1126/science.aan4665 |
Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity | |
Kornberg, Michael D.1; Bhargava, Pavan1; Kim, Paul M.2; Putluri, Vasanta3; Snowman, Adele M.4; Putluri, Nagireddy3,5; Calabresi, Peter A.1,4; Snyder, Solomon H.2,4,6 | |
2018-04-27 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 360期号:6387页码:449-453 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Activated immune cells undergo a metabolic switch to aerobic glycolysis akin to the Warburg effect, thereby presenting a potential therapeutic target in autoimmune disease. Dimethyl fumarate (DMF), a derivative of the Krebs cycle intermediate fumarate, is an immunomodulatory drug used to treat multiple sclerosis and psoriasis. Although its therapeutic mechanism remains uncertain, DMF covalently modifies cysteine residues in a process termed succination. We found that DMF succinates and inactivates the catalytic cysteine of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in mice and humans, both in vitro and in vivo. It thereby down-regulates aerobic glycolysis in activated myeloid and lymphoid cells, which mediates its anti-inflammatory effects. Our results provide mechanistic insight into immune modulation by DMF and represent a proof of concept that aerobic glycolysis is a therapeutic target in autoimmunity. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000430949600045 |
WOS关键词 | GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE ; T-CELLS ; MULTIPLE-SCLEROSIS ; EFFECTOR FUNCTION ; ACID ESTERS ; ACTIVATION ; INACTIVATION ; INFLAMMATION ; SUBSETS ; PATHWAY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/198517 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA; 2.Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA; 3.Baylor Coll Med, Adv Technol Core, Houston, TX 77030 USA; 4.Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA; 5.Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA; 6.Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA |
推荐引用方式 GB/T 7714 | Kornberg, Michael D.,Bhargava, Pavan,Kim, Paul M.,et al. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity[J]. SCIENCE,2018,360(6387):449-453. |
APA | Kornberg, Michael D..,Bhargava, Pavan.,Kim, Paul M..,Putluri, Vasanta.,Snowman, Adele M..,...&Snyder, Solomon H..(2018).Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity.SCIENCE,360(6387),449-453. |
MLA | Kornberg, Michael D.,et al."Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity".SCIENCE 360.6387(2018):449-453. |
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