Iron dysregulates APP processing accompanying with sAPPa cellular retention and β-secretase inhibition in rat cortical neurons

	Iron dysregulates APP processing accompanying with sAPPa cellular retention and β-secretase inhibition in rat cortical neurons
	Chen Yuting; Chen Wuyan; Huang Xiaotian; Xu Yechun; Zhang Haiyan
刊名	Acta Pharmacologica Sinica
	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
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
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292718]
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. Iron dysregulates APP processing accompanying with sAPPa cellular retention and β-secretase inhibition in rat cortical neurons[J]. Acta Pharmacologica Sinica,2018,39(2):177.
APA	Chen Yuting,Chen Wuyan,Huang Xiaotian,Xu Yechun,&Zhang Haiyan.(2018).Iron dysregulates APP processing accompanying with sAPPa cellular retention and β-secretase inhibition in rat cortical neurons.Acta Pharmacologica Sinica,39(2),177.
MLA	Chen Yuting,et al."Iron dysregulates APP processing accompanying with sAPPa cellular retention and β-secretase inhibition in rat cortical neurons".Acta Pharmacologica Sinica 39.2(2018):177.