Androgen alleviates neurotoxicity of beta-amyloid peptide (A beta) by promoting microglial clearance of A beta and inhibiting microglial inflammatory response to A beta
文献类型：期刊论文
| 作者 | Yao, Peng-Le2; Zhuo, Shu2; Mei, Hong2; Chen, Xiao-Fang2; Li, Na2; Zhu, Teng-Fei2; Chen, Shi-Ting2; Le, Ying-Ying1,2; Hou, Rui-Xing1; Wang, Ji-Ming3 |
| 刊名 | CNS NEUROSCIENCE & THERAPEUTICS
 |
| 出版日期 | 2017 |
| 卷号 | 23期号:11页码:855-865 |
| 关键词 | beta-amyloid peptide Alzheimer's disease androgen microglia |
| ISSN号 | 1755-5930 |
| DOI | 10.1111/cns.12757 |
| 文献子类 | Article |
| 英文摘要 | AimsLower androgen level in elderly men is a risk factor of Alzheimer's disease (AD). It has been reported that androgen reduces amyloid peptides (A) production and increases A degradation by neurons. Activated microglia are involved in AD by either clearing A deposits through uptake of A or releasing cytotoxic substances and pro-inflammatory cytokines. Here, we investigated the effect of androgen on A uptake and clearance and A-induced inflammatory response in microglia, on neuronal death induced by A-activated microglia, and explored underlying mechanisms. MethodsIntracellular and extracellular A were examined by immunofluorescence staining and Western blot. Amyloid peptides (A) receptors, A degrading enzymes, and pro-inflammatory cytokines were detected by RT-PCR, real-time PCR, and ELISA. Phosphorylation of MAP kinases and NF-B was examined by Western blot. ResultsWe found that physiological concentrations of androgen enhanced A(42) uptake and clearance, suppressed A(42)-induced IL-1 and TNF expression by murine microglia cell line N9 and primary microglia, and alleviated neuronal death induced by A(42)-activated microglia. Androgen administration also reduced A(42)-induced IL-1 expression and neuronal death in murine hippocampus. Mechanistic studies revealed that androgen promoted microglia to phagocytose and degrade A(42) through upregulating formyl peptide receptor 2 and endothelin-converting enzyme 1c expression, and inhibited A(42)-induced pro-inflammatory cytokines expression via suppressing MAPK p38 and NF-B activation by A(42), in an androgen receptor independent manner. ConclusionOur study demonstrates that androgen promotes microglia to phagocytose and clear A(42) and inhibits A(42)-induced inflammatory response, which may play an important role in reducing the neurotoxicity of A beta. |
| 学科主题 | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| WOS关键词 | ENDOTHELIN-CONVERTING ENZYME ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; INSULIN-DEGRADING ENZYME ; ALZHEIMERS-DISEASE ; TRANSGENIC MICE ; IMMUNE-SYSTEM ; UP-REGULATION ; 3XTG-AD MICE ; CELL UPTAKE ; TNF-ALPHA |
| 语种 | 英语 |
| WOS记录号 | WOS:000412579400001 |
| 出版者 | WILEY |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/881]  |
| 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.Soochow Univ, Ruihua Affiliated Hosp, Suzhou, Peoples R China; 2.Univ Chinese Acad Sci, Key Lab food safety Res, Chinese Acad Sci, Inst Nutr Sci,Shanghai Inst Biol Sci, Shanghai, Peoples R China; 3.NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21701 USA, |
| 推荐引用方式 GB/T 7714 | Yao, Peng-Le,Zhuo, Shu,Mei, Hong,et al. Androgen alleviates neurotoxicity of beta-amyloid peptide (A beta) by promoting microglial clearance of A beta and inhibiting microglial inflammatory response to A beta[J]. CNS NEUROSCIENCE & THERAPEUTICS,2017,23(11):855-865. |
| APA | Yao, Peng-Le.,Zhuo, Shu.,Mei, Hong.,Chen, Xiao-Fang.,Li, Na.,...&,.(2017).Androgen alleviates neurotoxicity of beta-amyloid peptide (A beta) by promoting microglial clearance of A beta and inhibiting microglial inflammatory response to A beta.CNS NEUROSCIENCE & THERAPEUTICS,23(11),855-865. |
| MLA | Yao, Peng-Le,et al."Androgen alleviates neurotoxicity of beta-amyloid peptide (A beta) by promoting microglial clearance of A beta and inhibiting microglial inflammatory response to A beta".CNS NEUROSCIENCE & THERAPEUTICS 23.11(2017):855-865. |
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。