Small molecule TBTC as a new selective retinoid X receptor alpha agonist improves behavioral deficit in Alzheimer's disease model mice
文献类型：期刊论文
| 作者 | Sun, Yanyan1; Fan, Jun2; Zhu, Zhiyuan2; Guo, Xiaodan2; Zhou, Tingting2; Duan, Wenhu2 ; Shen, Xu1,2
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| 刊名 | EUROPEAN JOURNAL OF PHARMACOLOGY
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| 出版日期 | 2015-09-05 |
| 卷号 | 762页码:202-213 |
| 关键词 | TBTC Retinoid X receptor alpha agonist beta-amyloid clearance Alzheimer's disease Daily living activity |
| ISSN号 | 0014-2999 |
| DOI | 10.1016/j.ejphar.2015.05.050 |
| 文献子类 | Article |
| 英文摘要 | Alzheimer's disease (AD) is a neurodegenerative disease, which is characterized by progressive cognitive impairments. The beta-amyloid (A beta)-induced neuroclegeneration is determined as the main pathogenesis of AD, and either decrease of All production or increase of All clearance is beneficial in the treatment of AD, while All clearance regulation seems to be more attractive as a promising therapeutic strategy against AD based on the fact that the insufficient clearance of A beta is tightly associated with the late onset of AD that is represented as the majority of AD cases. Here, we report that the small molecular compound, methyl 2-amino-6-(tert-butyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (TBTC), as a selective agonist of retinoid X receptor alpha (RXR alpha) can effectively activate the heterodimerization of RXR alpha with either liver X receptor a (LXR alpha) or peroxisome proliferator activated receptor gamma (PPAR gamma), stimulate the expressions of the genes of apoE, ABCA1 and ABCG1, and decrease A beta content both in cells and animal models. In addition, administration of TBTC (30 mg/kg/day) in the transgenic APP-PS1 mice could also reduce the formation of senile plaques and improve the daily living activity of the mice. Therefore, our findings have suggested that TBTC might hold the potential as a drug lead compound for the treatment of AD. (C) 2015 Elsevier B.V. All rights reserved. |
| WOS关键词 | AMELIORATES MEMORY IMPAIRMENT ; APPSWE/PS1 BIGENIC MODEL ; BETA-AMYLOID CLEARANCE ; CENTRAL-NERVOUS-SYSTEM ; APOLIPOPROTEIN-E ; NESTING-BEHAVIOR ; BIOLOGICAL EVALUATION ; MOUSE MODEL ; ABCA1 ; BRAIN |
| 资助项目 | National Natural Science Foundation of China[81373462] ; National Natural Science Foundation of China[81220108025] ; National Natural Science Foundation of China[91213306] ; National Natural Science Foundation of China[91413102] ; National Natural Science Foundation of China[81473141] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000359711100025 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276402]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Duan, Wenhu |
| 作者单位 | 1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Yanyan,Fan, Jun,Zhu, Zhiyuan,et al. Small molecule TBTC as a new selective retinoid X receptor alpha agonist improves behavioral deficit in Alzheimer's disease model mice[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2015,762:202-213. |
| APA | Sun, Yanyan.,Fan, Jun.,Zhu, Zhiyuan.,Guo, Xiaodan.,Zhou, Tingting.,...&Shen, Xu.(2015).Small molecule TBTC as a new selective retinoid X receptor alpha agonist improves behavioral deficit in Alzheimer's disease model mice.EUROPEAN JOURNAL OF PHARMACOLOGY,762,202-213. |
| MLA | Sun, Yanyan,et al."Small molecule TBTC as a new selective retinoid X receptor alpha agonist improves behavioral deficit in Alzheimer's disease model mice".EUROPEAN JOURNAL OF PHARMACOLOGY 762(2015):202-213. |
入库方式： OAI收割
来源：上海药物研究所
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