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DOI | 10.1038/s41467-019-10944-0 |
HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons | |
Kishinevsky, Sarah1,2,3,4; Wang, Tai3; Rodina, Anna3; Chung, Sun Young1,2; Xu, Chao3; Philip, John5; Taldone, Tony3; Joshi, Suhasini3; Alpaugh, Mary L.3,14; Bolaender, Alexander3; Gutbier, Simon6; Sandhu, Davinder7; Fattahi, Faranak1,2; Zimmer, Bastian1,2; Shah, Smit K.3; Chang, Elizabeth5; Inda, Carmen3,15; Koren, John, III3,16; Saurat, Nathalie G.1,2; Leist, Marcel6; Gross, Steven S.7; Seshan, Venkatraman E.8; Klein, Christine9; Tomishima, Mark J.1,2,10; Erdjument-Bromage, Hediye11,12; Neubert, Thomas A.11,12; Henrickson, Ronald C.5; Chiosis, Gabriela3,13; Studer, Lorenz1,2 | |
2019-07-09 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Germany |
英文摘要 | Environmental and genetic risk factors contribute to Parkinson's Disease (PD) pathogenesis and the associated midbrain dopamine (mDA) neuron loss. Here, we identify early PD pathogenic events by developing methodology that utilizes recent innovations in human pluripotent stem cells (hPSC) and chemical sensors of HSP90-incorporating chaperome networks. We show that events triggered by PD-related genetic or toxic stimuli alter the neuronal proteome, thereby altering the stress-specific chaperome networks, which produce changes detected by chemical sensors. Through this method we identify STAT3 and NF-kappa B signaling activation as examples of genetic stress, and phospho-tyrosine hydroxylase (TH) activation as an example of toxic stress-induced pathways in PD neurons. Importantly, pharmacological inhibition of the stress chaperome network reversed abnormal phospho-STAT3 signaling and phospho-TH-related dopamine levels and rescued PD neuron viability. The use of chemical sensors of chaperome networks on hPSC-derived lineages may present a general strategy to identify molecular events associated with neurodegenerative diseases. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000447697100003 |
WOS关键词 | NF-KAPPA-B ; PARKINSON-DISEASE ; MOLECULAR CHAPERONES ; ONSET PARKINSONISM ; PROTEIN ; PINK1 ; MITOCHONDRIAL ; CANCER ; INFLAMMATION ; STEM |
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/204448 |
专题 | 资源环境科学 |
作者单位 | 1.Mem Sloan Kettering Canc Ctr, Ctr Stem Cell Biol, 1275 York Ave,Box 256, New York, NY 10065 USA; 2.Mem Sloan Kettering Canc Ctr, Dev Biol Program, 1275 York Ave,Box 256, New York, NY 10065 USA; 3.Mem Sloan Kettering Canc Ctr, Program Chem Biol, 1275 York Ave, New York, NY 10065 USA; 4.Weill Cornell Med Coll, Weill Cornell Grad Sch Biomed Sci, Neurosci Grad Program, 1300 York Ave,Box 65, New York, NY 10065 USA; 5.Mem Sloan Kettering Canc Ctr, Prote Core Facil, 1275 York Ave, New York, NY 10065 USA; 6.Univ Konstanz, Doerenkamp Zbinden Chair Vitro Toxicol & Biomed, D-78464 Constance, Germany; 7.Weill Cornell Coll Med, Dept Pharmacol, 1300 York Ave, New York, NY 10065 USA; 8.Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA; 9.Univ Lubeck, Inst Neurogenet, D-23538 Lubeck, Germany; 10.Sloan Kettering Inst, SKI Stem Cell Res Facil, 1275 York Ave, New York, NY 10065 USA; 11.NYU, Dept Cell Biol, Sch Med, New York, NY 10016 USA; 12.NYU, Kimmel Ctr Biol & Med, Skirball Inst, Sch Med, New York, NY 10016 USA; 13.Mem Sloan Kettering Canc Ctr, Mem Hosp, Dept Med, 1275 York Ave, New York, NY 10065 USA; 14.Rowan Univ, Dept Mol & Cellular Biosci, 1275 York Ave, Glassboro, NJ 08028 USA; 15.CUNY, Hostos Community Coll, Bronx, NY 10453 USA; 16.Univ Notre Dame, Dept Biochem, Notre Dame, IN 46556 USA |
推荐引用方式 GB/T 7714 | Kishinevsky, Sarah,Wang, Tai,Rodina, Anna,et al. HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Kishinevsky, Sarah.,Wang, Tai.,Rodina, Anna.,Chung, Sun Young.,Xu, Chao.,...&Studer, Lorenz.(2019).HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons.NATURE COMMUNICATIONS,9. |
MLA | Kishinevsky, Sarah,et al."HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons".NATURE COMMUNICATIONS 9(2019). |
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