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DOI | 10.1126/science.aan4183 |
Defective cholesterol clearance limits remyelination in the aged central nervous system | |
Cantuti-Castelvetri, Ludovico1,2,3,4; Fitzner, Dirk1,5; Bosch-Queralt, Mar1,2,3,4; Weil, Marie-Theres1,6; Su, Minhui1,2,3,4; Sen, Paromita1; Ruhwedel, Torben7; Mitkovski, Miso8; Trendelenburg, George5; Luetjohann, Dieter9; Moebius, Wiebke6,7; Simons, Mikael1,2,3,4 | |
2018-02-09 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 359期号:6376页码:684-688 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany |
英文摘要 | Age-associated decline in regeneration capacity limits the restoration of nervous system functionality after injury. In a model for demyelination, we found that old mice fail to resolve the inflammatory response initiated after myelin damage. Aged phagocytes accumulated excessive amounts of myelin debris, which triggered cholesterol crystal formation and phagolysosomal membrane rupture and stimulated inflammasomes. Myelin debris clearance required cholesterol transporters, including apolipoprotein E. Stimulation of reverse cholesterol transport was sufficient to restore the capacity of old mice to remyelinate lesioned tissue. Thus, cholesterol-rich myelin debris can overwhelm the efflux capacity of phagocytes, resulting in a phase transition of cholesterol into crystals and thereby inducing a maladaptive immune response that impedes tissue regeneration. |
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:000425117700040 |
WOS关键词 | LIVER X RECEPTORS ; MULTIPLE-SCLEROSIS ; CNS REMYELINATION ; APOLIPOPROTEIN-E ; DIFFERENTIATION ; MACROPHAGES ; MICROGLIA ; CELLS |
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/197953 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Max Planck Inst Expt Med, D-37075 Gottingen, Germany; 2.Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany; 3.Tech Univ Munich, Inst Neuronal Cell Biol, D-80805 Munich, Germany; 4.German Ctr Neurodegenerat Dis DZNE, D-81377 Munich, Germany; 5.Univ Gottingen, Dept Neurol, Med Ctr, D-37075 Gottingen, Germany; 6.Ctr Nanoscale Microscopy & Mol Physiol Brain CNMP, D-37075 Gottingen, Germany; 7.Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany; 8.Max Planck Inst Expt Med, Light Microscopy Facil, D-37075 Gottingen, Germany; 9.Univ Bonn, Inst Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany |
推荐引用方式 GB/T 7714 | Cantuti-Castelvetri, Ludovico,Fitzner, Dirk,Bosch-Queralt, Mar,et al. Defective cholesterol clearance limits remyelination in the aged central nervous system[J]. SCIENCE,2018,359(6376):684-688. |
APA | Cantuti-Castelvetri, Ludovico.,Fitzner, Dirk.,Bosch-Queralt, Mar.,Weil, Marie-Theres.,Su, Minhui.,...&Simons, Mikael.(2018).Defective cholesterol clearance limits remyelination in the aged central nervous system.SCIENCE,359(6376),684-688. |
MLA | Cantuti-Castelvetri, Ludovico,et al."Defective cholesterol clearance limits remyelination in the aged central nervous system".SCIENCE 359.6376(2018):684-688. |
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