MCC950 ameliorates the dementia symptom at the early age of line M83 mouse and reduces hippocampal alpha-synuclein accumulation
文献类型：期刊论文
| 作者 | Ren, Yu2,3; Wang, Qing1,2; Yang, Zexian1,2; Feng, Linyin1,2,3 ; Zhang, Yu2
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| 刊名 | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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| 出版日期 | 2022-06-30 |
| 卷号 | 611页码:23-30 |
| ISSN号 | 0006-291X |
| 关键词 | MCC950 Line M83 Dementia A53T alpha-synuclein Autophagy |
| DOI | 10.1016/j.bbrc.2022.04.076 |
| 通讯作者 | Feng, Linyin(lyfeng@simm.ac.cn) ; Zhang, Yu(zhangyu5@simm.ac.cn) |
| 英文摘要 | Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia after Alzheimer's disease (AD). Neuroinflammation plays an important role in neurodegenerative diseases. It is urgent to unravel the pathogenesis of DLB and find potential therapeutic drugs. Here, we investigated the pharmacological effects of the NLRP3 inflammasome inhibitor MCC950 in A53T alpha-synuclein transgenic line M83 mice aged 4 months. The behavioral tests including Y-maze, Barnes maze, nest building and Rotarod showed that MCC950 significantly improved the cognitive dysfunction symptom without affecting the motor coordination after consecutive intragastric administration every day for 5 weeks. Furthermore, immunostaining or immunoblotting experiments on the hippocampal tissue were performed, and the results suggested that MCC950 not only inhibited the expression of NLRP3, and suppressed the activation of astrocytes and microglia, but also promoted the mTOR-mediated autophagy pathway to reduce human alpha-synuclein accumulation. Our findings further demonstrate that line M83 mice may be used as an animal model for DLB research, and can provide preclinical evidences for the development of MCC950 as a promising therapeutic drug. (C) 2022 Elsevier Inc. All rights reserved. |
| WOS关键词 | AUTOPHAGY ; NEURODEGENERATION ; INHIBITION ; SUPPRESSES |
| 资助项目 | National Natural Science Foundation of China[82104140] ; National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology[2018ZX09711002-003-013] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| WOS记录号 | WOS:000860994800007 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302607]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Feng, Linyin; Zhang, Yu |
| 作者单位 | 1.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Ctr Neurol & Psychiat Res & Drug Discovery CNPRDD, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210023, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ren, Yu,Wang, Qing,Yang, Zexian,et al. MCC950 ameliorates the dementia symptom at the early age of line M83 mouse and reduces hippocampal alpha-synuclein accumulation[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2022,611:23-30. |
| APA | Ren, Yu,Wang, Qing,Yang, Zexian,Feng, Linyin,&Zhang, Yu.(2022).MCC950 ameliorates the dementia symptom at the early age of line M83 mouse and reduces hippocampal alpha-synuclein accumulation.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,611,23-30. |
| MLA | Ren, Yu,et al."MCC950 ameliorates the dementia symptom at the early age of line M83 mouse and reduces hippocampal alpha-synuclein accumulation".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 611(2022):23-30. |
入库方式： OAI收割
来源：上海药物研究所
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