IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease
文献类型：期刊论文
| 作者 | Yan, Cheng1,2; Liu, Jingqi2; Sun, Ying2; Song, Haiyun2; Zhan, Lixing2; Liu, Jingnan2,3; Gao, Jiamei3; Zhang, Lei3; Gao, Guanjun3; Zhang, Lei4 |
| 刊名 | CELL DEATH & DISEASE
 |
| 出版日期 | 2019 |
| 卷号 | 10期号:-页码:800 |
| ISSN号 | 2041-4889 |
| DOI | 10.1038/s41419-019-2039-6 |
| 文献子类 | Article |
| 英文摘要 | Abnormal aggregation of misfolded pathological proteins in neurons is a prominent feature of neurodegenerative disorders including Parkinson's disease (PD). Perturbations of proteostasis at the endoplasmic reticulum (ER) triggers ER stress, activating the unfolded protein response (UPR). Chronic ER stress is thought to underlie the death of neurons during the neurodegenerative progression, but the precise mechanism by which the UPR pathways regulate neuronal cell fate remains incompletely understood. Here we report a critical neurodegenerative role for inositol-requiring enzyme 1 (IRE1), the evolutionarily conserved ER stress sensor, in a Drosophila model of PD. We found that IRE1 was hyperactivated upon accumulation of alpha-synuclein in the fly photoreceptor neurons. Ectopic overexpression of IRE1 was sufficient to trigger autophagy-dependent neuron death in an XBP1-independent, JNK-dependent manner. Furthermore, IRE1 was able to promote dopaminergic neuron loss, progressive locomotor impairment, and shorter lifespan, whereas blocking IRE1 or ATG7 expression remarkably ameliorated the progression of alpha-synuclein-caused Parkinson's disease. These results provide in vivo evidence demonstrating that the IRE1 pathway drives PD progression through coupling ER stress to autophagy-dependent neuron death. |
| 学科主题 | Genetics & Heredity |
| WOS关键词 | UNFOLDED-PROTEIN-RESPONSE ; ENDOPLASMIC-RETICULUM STRESS ; ALPHA-SYNUCLEIN TOXICITY ; CELL-DEATH ; ER STRESS ; CASPASE DRONC ; AGGREGATION ; DEGRADATION ; SUPPRESSION ; ACTIVATION |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31641108 |
| WOS记录号 | WOS:000491340400006 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/833]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Xinxiang Univ, Sch Med, Xinxiang 453003, Henan, Peoples R China, 2.Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 4.Chinese Acad Sci, Inst Biochem & Cell Biol, Innovat Ctr Cell Signaling Network,Shanghai Inst, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai 200031, Peoples R China; 5.Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China; 6.Shanghai Univ Chinese Tradit Med, Basic Med Coll, Dept Biochem, Shanghai 201203, Peoples R China; 7.Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Hubei, Peoples R China; 8.Wuhan Univ, Inst Adv Studies, Wuhan 430072, Hubei, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yan, Cheng,Liu, Jingqi,Sun, Ying,et al. IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease[J]. CELL DEATH & DISEASE,2019,10(-):800. |
| APA | Yan, Cheng.,Liu, Jingqi.,Sun, Ying.,Song, Haiyun.,Zhan, Lixing.,...&,.(2019).IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease.CELL DEATH & DISEASE,10(-),800. |
| MLA | Yan, Cheng,et al."IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease".CELL DEATH & DISEASE 10.-(2019):800. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。