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| DOI | 10.1126/science.aat8407 |
| Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson's disease | |
| Kam, Tae-In1,2,3,4; Mao, Xiaobo1,2,3,4; Park, Hyejin1,2,3,4; Chou, Shih-Ching1,2,5; Karuppagounder, Senthilkumar S.1,2,3,4; Umanah, George Essien1,2,3; Yun, Seung Pil1,2,3,4; Brahmachari, Saurav1,2,3,4; Panicker, Nikhil1,2,3,4; Chen, Rong1,2,3,4; Andrabi, Shaida A.1,2,3,14; Qi, Chen1,2,3,6; Poirier, Guy G.7; Pletnikova, Olga8; Troncoso, Juan C.3,8; Bekris, Lynn M.9; Leverenz, James B.10,11; Pantelyat, Alexander3; Ko, Han Seok1,2,3,4; Rosenthal, Liana S.3; Dawson, Ted M.1,2,3,4,5,12; Dawson, Valina L.1,2,3,4,12,13 | |
| 2018-11-02 | |
| 发表期刊 | SCIENCE
 |
| ISSN | 0036-8075 |
| EISSN | 1095-9203 |
| 出版年 | 2018 |
| 卷号 | 362期号:6414页码:557-+ |
| 文章类型 | Article |
| 语种 | 英语 |
| 国家 | USA; Peoples R China; Canada |
| 英文摘要 | The pathologic accumulation and aggregation of alpha-synuclein (alpha-syn) underlies Parkinson's disease (PD). The molecular mechanisms by which pathologic alpha-syn causes neurodegeneration in PD are not known. Here, we found that pathologic alpha-syn activates poly(adenosine 5'-diphosphate-ribose) (PAR) polymerase-1 (PARP-1), and PAR generation accelerates the formation of pathologic alpha-syn, resulting in cell death via parthanatos. PARP inhibitors or genetic deletion of PARP-1 prevented pathologic alpha-syn toxicity. In a feed-forward loop, PAR converted pathologic alpha-syn to a more toxic strain. PAR levels were increased in the cerebrospinal fluid and brains of patients with PD, suggesting that PARP activation plays a role in PD pathogenesis. Thus, strategies aimed at inhibiting PARP-1 activation could hold promise as a disease-modifying therapy to prevent the loss of dopamine neurons in PD. |
| 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:000450460000037 |
| WOS关键词 | CELL-DEATH ; MECHANISMS ; AGGREGATION ; STRAINS ; PROTEIN |
| WOS类目 | Multidisciplinary Sciences |
| WOS研究方向 | Science & Technology - Other Topics |
| 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/199985 |
| 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, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD 21205 USA; 2.Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA; 3.Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA; 4.Adrienne Helis Malvin Med Res Fdn, New Orleans, LA 70130 USA; 5.Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA; 6.Shanghai Jiao Tong Univ, Dept Neurol, Xin Hua Hosp, Sch Med, Shanghai 200092, Peoples R China; 7.Univ Laval, Fac Med, Ctr Rech, CHU Quebec Pavillon,CHUL, Quebec City, PQ G1V 4G2, Canada; 8.Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, Baltimore, MD 21205 USA; 9.Cleveland Clin, Lerner Res Inst, Genom Med, Cleveland, OH 44195 USA; 10.Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Neurol Inst, Cleveland, OH 44195 USA; 11.Cleveland Clin, Dept Neurol, Cleveland, OH 44195 USA; 12.Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA; 13.Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA; 14.Univ Alabama Birmingham, Sch Med, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA |
| 推荐引用方式 GB/T 7714 | Kam, Tae-In,Mao, Xiaobo,Park, Hyejin,et al. Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson's disease[J]. SCIENCE,2018,362(6414):557-+. |
| APA | Kam, Tae-In.,Mao, Xiaobo.,Park, Hyejin.,Chou, Shih-Ching.,Karuppagounder, Senthilkumar S..,...&Dawson, Valina L..(2018).Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson's disease.SCIENCE,362(6414),557-+. |
| MLA | Kam, Tae-In,et al."Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson's disease".SCIENCE 362.6414(2018):557-+. |
| 条目包含的文件 | 条目无相关文件。 | |||||
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