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DOI | 10.1038/s41467-018-03328-3 |
Elongator mutation in mice induces neurodegeneration and ataxia-like behavior | |
Kojic, Marija1; Gaik, Monika2; Kiska, Bence1; Salerno-Kochan, Anna2,3; Hunt, Sarah4; Tedoldi, Angelo4; Mureev, Sergey1; Jones, Alun1; Whittle, Belinda5; Genovesi, Laura A.1; Adolphe, Christelle1; Brown, Darren L.1; Stow, Jennifer L.1; Alexandrov, Kirill1; Sah, Pankaj4; Glatt, Sebastian2; Wainwright, Brandon J.1 | |
2018-08-10 | |
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 | Australia; Poland |
英文摘要 | Cerebellar ataxias are severe neurodegenerative disorders with an early onset and progressive and inexorable course of the disease. Here, we report a single point mutation in the gene encoding Elongator complex subunit 6 causing Purkinje neuron degeneration and an ataxia-like phenotype in the mutant wobbly mouse. This mutation destabilizes the complex and compromises its function in translation regulation, leading to protein misfolding, proteotoxic stress, and eventual neuronal death. In addition, we show that substantial micro-gliosis is triggered by the NLRP3 inflammasome pathway in the cerebellum and that blocking NLRP3 function in vivo significantly delays neuronal degeneration and the onset of ataxia in mutant animals. Our data provide a mechanistic insight into the pathophysiology of a cerebellar ataxia caused by an Elongator mutation, substantiating the increasing body of evidence that alterations of this complex are broadly implicated in the onset of a number of diverse neurological disorders. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000441306000002 |
WOS关键词 | TRANSFER-RNA ; FAMILIAL DYSAUTONOMIA ; ALZHEIMERS-DISEASE ; NLRP3 INFLAMMASOME ; GENE ; ACTIVATION ; BETA ; ELP3 ; OPTIMIZATION ; TRANSLATION |
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/203695 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia; 2.Jagiellonian Univ, Max Planck Res Grp, Malopolska Ctr Biotechnol, Krakow, Poland; 3.Postgrad Sch Mol Med, Warsaw, Poland; 4.Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia; 5.Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia |
推荐引用方式 GB/T 7714 | Kojic, Marija,Gaik, Monika,Kiska, Bence,et al. Elongator mutation in mice induces neurodegeneration and ataxia-like behavior[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Kojic, Marija.,Gaik, Monika.,Kiska, Bence.,Salerno-Kochan, Anna.,Hunt, Sarah.,...&Wainwright, Brandon J..(2018).Elongator mutation in mice induces neurodegeneration and ataxia-like behavior.NATURE COMMUNICATIONS,9. |
MLA | Kojic, Marija,et al."Elongator mutation in mice induces neurodegeneration and ataxia-like behavior".NATURE COMMUNICATIONS 9(2018). |
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