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Activation of Necroptosis in Multiple Sclerosis
文献类型：期刊论文
| 作者 | Ofengeim, Dimitry2; Ito, Yasushi2; Najafov, Ayaz2; Zhang, Yaoyang3; Shan, Bing3; DeWitt, Judy Park2; Ye, Juanying5; Zhang, Xumin5; Chang, Ansi3; Vakifahmetoglu-Norberg, Helin2 |
| 刊名 | CELL REPORTS
 |
| 出版日期 | 2015-03-24 |
| 卷号 | 10期号:11页码:1836-1849 |
| ISSN号 | 2211-1247 |
| DOI | 10.1016/j.celrep.2015.02.051 |
| 文献子类 | Article |
| 英文摘要 | Multiple sclerosis (MS), a common neurodegenerative disease of the CNS, is characterized by the loss of oligodendrocytes and demyelination. Tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine implicated in MS, can activate necroptosis, a necrotic cell death pathway regulated by RIPK1 and RIPK3 under caspase-8-deficient conditions. Here, we demonstrate defective caspase-8 activation, as well as activation of RIPK1, RIPK3, and MLKL, the hallmark mediators of necroptosis, in the cortical lesions of human MS pathological samples. Furthermore, we show that MS pathological samples are characterized by an increased insoluble proteome in common with other neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Finally, we show that necroptosis mediates oligodendrocyte degeneration induced by TNF-alpha and that inhibition of RIPK1 protects against oligodendrocyte cell death in two animal models of MS and in culture. Our findings demonstrate that necroptosis is involved in MS and suggest that targeting RIPK1 may represent a therapeutic strategy for MS. |
| WOS关键词 | MIXED LINEAGE KINASE ; DOMAIN-LIKE PROTEIN ; NECROTIC CELL-DEATH ; RIP1 KINASE ; PROGRAMMED NECROSIS ; IN-VIVO ; SIGNALING COMPLEX ; TNF-ALPHA ; DEMYELINATION ; INFLAMMATION |
| 资助项目 | NINDS[1R01NS082257] ; NIA[1R01AG047231] ; Ellison Medical Foundation[00000000] ; Molecular Biology of Neurodegeneration Training Grant from the NINDS (PI: Bruce Yankner)[00000000] ; National Multiple Sclerosis Society[00000000] ; Daiichi Sankyo Foundation of Life Science[00000000] ; Nakatomi Foundation[00000000] ; Mochida Memorial Foundation for Medical and Pharmaceutical Research[00000000] ; Japan Society for the Promotion of Science[00000000] ; Brazilian CNPq Sandwich Program[00000000] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000351779600006 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276601]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Yuan, Junying |
| 作者单位 | 1.Cleveland Clin, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA; 2.Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA; 3.Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 200032, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 5.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ofengeim, Dimitry,Ito, Yasushi,Najafov, Ayaz,et al. Activation of Necroptosis in Multiple Sclerosis[J]. CELL REPORTS,2015,10(11):1836-1849. |
| APA | Ofengeim, Dimitry.,Ito, Yasushi.,Najafov, Ayaz.,Zhang, Yaoyang.,Shan, Bing.,...&Yuan, Junying.(2015).Activation of Necroptosis in Multiple Sclerosis.CELL REPORTS,10(11),1836-1849. |
| MLA | Ofengeim, Dimitry,et al."Activation of Necroptosis in Multiple Sclerosis".CELL REPORTS 10.11(2015):1836-1849. |
入库方式： OAI收割
来源：上海药物研究所
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