Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease

doi:10.1016/j.neurobiolaging.2013.11.004

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease
	Huang, Xiao-Tian 1,3; Qian, Zhong-Ming 2; He, Xuan 1; Gong, Qi 1; Wu, Ka-Chun 1; Jiang, Li-Rong 2; Lu, Li-Na 1; Zhu, Zhou-jing 1; Zhang, Hai-Yan3 ; Yung, Wing-Ho 1
刊名	NEUROBIOLOGY OF AGING
	2014-05
卷号	35 期号:5 页码:1045-1054
关键词	Huperzine A Alzheimer's disease Brain iron Transferrin receptor 1 Double transgenic APPswe/PS1dE9 mice (APP/PS mice) The neuronal amyloid precursor protein (APP)
ISSN号	0197-4580
DOI	10.1016/j.neurobiolaging.2013.11.004
文献子类	Article
英文摘要	Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States. In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties. However, the relevant mechanism is unknown. Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation. HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice. However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet. In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease. (C) 2014 Elsevier Inc. All rights reserved.
资助项目	Competitive Earmarked Grants of The Hong Kong Research Grants Council[GRF 466713] ; National Basic Research Program of China (973 Program)[2011CB510004] ; General Grant of National Natural Science Foundation of China (NSFC)[31271132-2012] ; General Grant of National Natural Science Foundation of China (NSFC)[31371092-2013] ; Key Project Grant of NSFC[31330035-2013] ; Chinese University of Hong Kong[4054042]
WOS关键词	AMYLOID-PRECURSOR-PROTEIN ; TRANSFERRIN-BOUND IRON ; TRANSGENIC MICE ; RAT-BRAIN ; NEURODEGENERATIVE DISORDERS ; EXPRESSION ; CERULOPLASMIN ; TRANSPORT ; PATHWAYS ; KINASE
WOS研究方向	Geriatrics & Gerontology ; Neurosciences & Neurology
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000332308300011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277108]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ke, Ya
作者单位	1.Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China; 2.Fudan Univ, Sch Pharm, Neuropharmacol Lab, Shanghai 200433, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Huang, Xiao-Tian,Qian, Zhong-Ming,He, Xuan,et al. Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease[J]. NEUROBIOLOGY OF AGING,2014,35(5):1045-1054.
APA	Huang, Xiao-Tian.,Qian, Zhong-Ming.,He, Xuan.,Gong, Qi.,Wu, Ka-Chun.,...&Ke, Ya.(2014).Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease.NEUROBIOLOGY OF AGING,35(5),1045-1054.
MLA	Huang, Xiao-Tian,et al."Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease".NEUROBIOLOGY OF AGING 35.5(2014):1045-1054.