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DOI | 10.1126/science.aam9080 |
Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease | |
Burbulla, Lena F.1,2; Song, Pingping1; Mazzulli, Joseph R.1,2; Zampese, Enrico3; Wong, Yvette C.1; Jeon, Sohee1; Santos, David P.1; Blanz, Judith1; Obermaier, Carolin D.4,5,6,7; Strojny, Chelsee1; Savas, Jeffrey N.1; Kiskinis, Evangelos1; Zhuang, Xiaoxi8; Kruger, Rejko4,5,7,9; Surmeier, D. James; Krainc, Dimitri1,2 | |
2017-09-22 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 357期号:6357页码:1255-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Germany; Luxembourg |
英文摘要 | Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and a-synuclein accumulation. This toxic cascade was observed in human, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism. Increasing dopamine synthesis or a-synuclein amounts in mouse midbrain neurons recapitulated pathological phenotypes observed in human neurons. Thus, dopamine oxidation represents an important link between mitochondrial and lysosomal dysfunction in PD pathogenesis. |
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:000411337700037 |
WOS关键词 | ALPHA-SYNUCLEIN ; SUBSTANTIA-NIGRA ; GLUCOCEREBROSIDASE ; DJ-1 ; PACEMAKING |
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/196929 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Northwestern Univ Feinberg, Sch Med, Dept Neurol, Chicago, IL 60611 USA; 2.Harvard Med Sch, MassGen Inst Neurodegenerat, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA; 3.Northwestern Univ Feinberg, Sch Med, Dept Physiol, Chicago, IL 60611 USA; 4.Univ Tubingen, Dept Neurodegenerat Dis, Tubingen, Germany; 5.Univ Tubingen, Hertie Inst Clin Brain Res, DZNE, German Ctr Neurodegenerat Dis, Tubingen, Germany; 6.Univ Tubingen, Grad Sch Cellular & Mol Neurosci, Tubingen, Germany; 7.Univ Luxembourg, Luxembourg Ctr Syst Biomed, Clin & Expt Neurosci, Luxembourg, Luxembourg; 8.Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA; 9.Ctr Hosp Luxembourg, Luxembourg, Luxembourg |
推荐引用方式 GB/T 7714 | Burbulla, Lena F.,Song, Pingping,Mazzulli, Joseph R.,et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease[J]. SCIENCE,2017,357(6357):1255-+. |
APA | Burbulla, Lena F..,Song, Pingping.,Mazzulli, Joseph R..,Zampese, Enrico.,Wong, Yvette C..,...&Krainc, Dimitri.(2017).Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease.SCIENCE,357(6357),1255-+. |
MLA | Burbulla, Lena F.,et al."Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease".SCIENCE 357.6357(2017):1255-+. |
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