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DOI | 10.1038/s41467-017-00613-5 |
Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1 | |
Garcia-Morales, Victoria1,2; Rodriguez-Bey, Guillermo1; Gomez-Perez, Laura1; Dominguez-Vias, German1,2; Gonzalez-Forero, David1,2; Portillo, Federico1,2; Campos-Caro, Antonio2,3; Gento-Caro, Angela1,2; Issaoui, Noura1; Soler, Rosa M.4; Garcera, Ana4; Moreno-Lopez, Bernardo1,2 | |
2019-08-22 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | Spain |
英文摘要 | Disruption in membrane excitability contributes to malfunction and differential vulnerability of specific neuronal subpopulations in a number of neurological diseases. The adaptor protein p11, and background potassium channel TASK1, have overlapping distributions in the CNS. Here, we report that the transcription factor Sp1 controls p11 expression, which impacts on excitability by hampering functional expression of TASK1. In the SOD1-G93A mouse model of ALS, Sp1-p11-TASK1 dysregulation contributes to increased excitability and vulnerability of motor neurons. Interference with either Sp1 or p11 is neuroprotective, delaying neuron loss and prolonging lifespan in this model. Nitrosative stress, a potential factor in human neurodegeneration, stimulated Sp1 expression and human p11 promoter activity, at least in part, through a Sp1-binding site. Disruption of Sp1 or p11 also has neuroprotective effects in a traumatic model of motor neuron degeneration. Together our work suggests the Sp1-p11-TASK1 pathway is a potential target for treatment of degeneration of motor neurons. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000482183300008 |
WOS关键词 | AMYOTROPHIC-LATERAL-SCLEROSIS ; NITRIC-OXIDE SYNTHASE ; MOUSE MODEL ; POTASSIUM CHANNEL ; ANTITUMOR-ACTIVITY ; MOTONEURONS ; INHIBITION ; EXCITABILITY ; TRANSCRIPTION ; VULNERABILITY |
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/203515 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Cadiz, Fac Med, Area Fisiol, Grp Neurodegenerac & Neurorreparac GRUNEDERE, Cadiz 11003, Spain; 2.Inst Invest & Innovac Biomed Cadiz INiBICA, Cadiz, Spain; 3.Hosp Univ Puerta Mar, Unidad Invest, Cadiz, Spain; 4.Univ Lleida, IRBLLEIDA, Dept Med Expt, Unitat Senyalitzacio Neuronal, Lleida, Spain |
推荐引用方式 GB/T 7714 | Garcia-Morales, Victoria,Rodriguez-Bey, Guillermo,Gomez-Perez, Laura,et al. Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Garcia-Morales, Victoria.,Rodriguez-Bey, Guillermo.,Gomez-Perez, Laura.,Dominguez-Vias, German.,Gonzalez-Forero, David.,...&Moreno-Lopez, Bernardo.(2019).Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1.NATURE COMMUNICATIONS,10. |
MLA | Garcia-Morales, Victoria,et al."Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1".NATURE COMMUNICATIONS 10(2019). |
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