irondysregulatesappprocessingaccompanyingwithsappacellularretentionandsecretaseinhibitioninratcorticalneurons
文献类型：期刊论文
| 作者 | Chen Yuting; Chen Wuyan; Huang Xiaotian; Xu Yechun ; Zhang Haiyan
|
| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2018 |
| 卷号 | 39期号:2页码:177 |
| 关键词 | iron neurons amyloid precursor protein sAPPα β-amyloid β-secretase Alzheimer's disease |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2017.113 |
| 英文摘要 | Amyloid precursor protein (APP) and iron both play pivotal roles in the central nervous system, but whether and how iron influences the processing of endogenous APP in neurons remain unclear. Here, we investigated the regulatory effects and underlying mechanisms of iron on non-amyloidogenic and amyloidogenic processing of APP in rat primary cortical neurons. Treatment of the neurons with ferric ammonium citrate (FAC,100 μmol/L) markedly facilitated the non-amyloidogenic processing of APP, as evidenced by a robust increase in a-secretase-derived carboxy-terminal fragment a (CTFa). Furthermore, the distribution of sAPPa was altered after iron treatment, and sAPPa remained in the cellular lysates instead of being secreted into the extracellular milieu. Moreover, the levels of APP amyloidogenic products, including sAPPβ and Aβ were both decreased. We further revealed that FAC did not alter the expression of β-secretase,but significantly suppressed its enzymatic activity in iron-treated neurons. In a cell-free β-secretase activity assay, FAC dose-dependently inhibited the activity of purified β-secretase with an IC_(50) value of 21.67 μmol/L. Our data provide the first evidence that iron overload alters the neuronal sAPPa distribution and directly inhibits β-secretase activity. These findings shed light on the regulatory mechanism of bio-metals on APP processing. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/288453]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Chen Yuting,Chen Wuyan,Huang Xiaotian,et al. irondysregulatesappprocessingaccompanyingwithsappacellularretentionandsecretaseinhibitioninratcorticalneurons[J]. actapharmacologicasinica,2018,39(2):177. |
| APA | Chen Yuting,Chen Wuyan,Huang Xiaotian,Xu Yechun,&Zhang Haiyan.(2018).irondysregulatesappprocessingaccompanyingwithsappacellularretentionandsecretaseinhibitioninratcorticalneurons.actapharmacologicasinica,39(2),177. |
| MLA | Chen Yuting,et al."irondysregulatesappprocessingaccompanyingwithsappacellularretentionandsecretaseinhibitioninratcorticalneurons".actapharmacologicasinica 39.2(2018):177. |
入库方式： OAI收割
来源：上海药物研究所
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