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| DOI | 10.1126/science.aaf3934 |
| beta(2)-Adrenoreceptor is a regulator of the alpha-synuclein gene driving risk of Parkinson's disease | |
| Mittal, Shuchi1,2,3,4,5; Bjornevik, Kjetil6,7; Im, Doo Soon8; Flierl, Adrian9; Dong, Xianjun1,2,3,4,5; Locascio, Joseph J.1,2,10; Abo, Kristine M.1,2; Long, Elizabeth1,2; Jin, Ming3,4,5; Xu, Bing11; Xiang, Yang K.11; Rochet, Jean-Christophe12; Engeland, Anders6,13; Rizzu, Patrizia14; Heutink, Peter14; Bartels, Tim3,4,5; Selkoe, Dennis J.3,4,5; Caldarone, Barbara J.5,15; Glicksman, Marcie A.15; Khurana, Vikram3,4,5,16; Schule, Birgitt9; Park, David S.8; Riise, Trond6,7; Scherzer, Clemens R.1,2,3,4,5 | |
| 2017-09-01 | |
| 发表期刊 | SCIENCE
 |
| ISSN | 0036-8075 |
| EISSN | 1095-9203 |
| 出版年 | 2017 |
| 卷号 | 357期号:6354页码:891-897 |
| 文章类型 | Article |
| 语种 | 英语 |
| 国家 | USA; Norway; Canada; Germany |
| 英文摘要 | Copy number mutations implicate excess production of a-synuclein as a possibly causative factor in Parkinson's disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the beta 2-adrenoreceptor (beta 2AR) is a regulator of the a-synuclein gene (SNCA). beta 2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation of its promoter and enhancers. Over 11 years of follow-up in 4 million Norwegians, the beta 2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD (rate ratio, 0.66; 95% confidence interval, 0.58 to 0.76). Conversely, a beta 2AR antagonist correlated with increased risk. beta 2AR activation protected model mice and patient-derived cells. Thus, beta 2AR is linked to transcription of a-synuclein and risk of PD in a ligand-specific fashion and constitutes a potential target for therapies. |
| 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:000408734900037 |
| WOS关键词 | EXPRESSION ; CLENBUTEROL ; TOXICITY ; PATHWAY ; ACID |
| 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/196775 |
| 专题 | 地球科学 资源环境科学 气候变化 |
| 作者单位 | 1.Harvard Med Sch, Neurogen Lab, Boston, MA 02115 USA; 2.Brigham & Womens Hosp, Boston, MA 02115 USA; 3.Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA; 4.Harvard Med Sch, Boston, MA 02115 USA; 5.Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA; 6.Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway; 7.Haukeland Hosp, Dept Neurol, Norwegian Multiple Sclerosis Competence Ctr, Bergen, Norway; 8.Univ Ottawa, Brain & Mind Res Inst, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada; 9.Parkinsons Inst & Clin Ctr, Sunnyvale, CA 94085 USA; 10.Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA; 11.Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA; 12.Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA; 13.Norwegian Inst Publ Hlth, Dept Pharmacoepidemiol, Oslo, Norway; 14.German Ctr Neurodegenerat Dis DZNE, D-72076 Tubingen, Germany; 15.Harvard Med Sch, Harvard NeuroDiscovery Ctr, Boston, MA 02115 USA; 16.Harvard Stem Cell Inst, Cambridge, MA 02138 USA |
| 推荐引用方式 GB/T 7714 | Mittal, Shuchi,Bjornevik, Kjetil,Im, Doo Soon,et al. beta(2)-Adrenoreceptor is a regulator of the alpha-synuclein gene driving risk of Parkinson's disease[J]. SCIENCE,2017,357(6354):891-897. |
| APA | Mittal, Shuchi.,Bjornevik, Kjetil.,Im, Doo Soon.,Flierl, Adrian.,Dong, Xianjun.,...&Scherzer, Clemens R..(2017).beta(2)-Adrenoreceptor is a regulator of the alpha-synuclein gene driving risk of Parkinson's disease.SCIENCE,357(6354),891-897. |
| MLA | Mittal, Shuchi,et al."beta(2)-Adrenoreceptor is a regulator of the alpha-synuclein gene driving risk of Parkinson's disease".SCIENCE 357.6354(2017):891-897. |
| 条目包含的文件 | 条目无相关文件。 | |||||
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