Involvement of Intracellular and Mitochondrial A beta in the Ameliorative Effects of Huperzine A against Oligomeric A beta(42)-Induced Injury in Primary Rat Neurons

doi:10.1371/journal.pone.0128366

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

	Involvement of Intracellular and Mitochondrial A beta in the Ameliorative Effects of Huperzine A against Oligomeric A beta(42)-Induced Injury in Primary Rat Neurons
	Lei, Yun 2; Yang, Ling 2; Ye, Chun Yan 2; Qin, Ming Yan 1; Yang, Huai Yu 1; Jiang, Hua Liang 1; Tang, Xi Can 1; Zhang, Hai Yan 1
刊名	PLOS ONE
	2015-05-29
卷号	10 期号:5
ISSN号	1932-6203
DOI	10.1371/journal.pone.0128366
文献子类	Article
英文摘要	Considerable studies indicate huperzine A is a promising natural product to suppress neuronal damages induced by beta-amyloid (A beta), a key pathogenic event in the Alzheimer's disease (AD). As an extension, the present study for the first time explored whether the beneficial profiles of huperzine A against oligomeric A beta(42) induced neurotoxicity are associated with the accumulation and detrimental function of intraneuronal/mitochondrial A beta, on the basis of the emerging evidence that intracellular A beta is more relevant to AD progression as compared with extracellular A beta. Huperzine A treatment was shown to significantly attenuate the neurotoxicity of oligomeric A beta(42), as demonstrated by increased neuronal viability. Interestingly, our results proved that exogenous A beta(42) could accumulate intraneuronally in a dose-and time-dependent manner, while huperzine A treatment markedly reduced the level of intracellular A beta(42). Moreover, huperzine A treatment rescued mitochondrial dysfunction induced by oligomeric A beta(42), including adenosine triphosphate (ATP) reduction, reactive oxygen species (ROS) overproduction and membrane potential depolarization. Further study demonstrated that huperzine A also significantly reduced the level of A beta(42) in the mitochondria-enriched subcellular fractions, as well as the A beta(42) fluorescent signals colocalized with mitochondrial marker. This study indicates that interfering intracellular A beta especially mitochondrial A beta accumulation, together with ameliorating A beta-associated mitochondrial dysfunction, may contribute to the protective effects of huperzine A against A beta neurotoxicity. Above results may shed more light on the pharmacological mechanisms of huperzine A and provide important clues for discovering novel therapeutic strategies for AD.
资助项目	National Natural Science Foundation of China[81173034] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2012ZX09301001-004] ; Ministry of Science and Technology of China[2011CB510004]
WOS关键词	AMYLOID-BETA ; ALZHEIMERS-DISEASE ; CELL-DEATH ; IN-VITRO ; OXIDATIVE STRESS ; TRANSGENIC MICE ; ACCUMULATION ; PEPTIDE ; DYSFUNCTION ; PROTEIN
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000355319400087
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276518]
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	Zhang, Hai Yan
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Lei, Yun,Yang, Ling,Ye, Chun Yan,et al. Involvement of Intracellular and Mitochondrial A beta in the Ameliorative Effects of Huperzine A against Oligomeric A beta(42)-Induced Injury in Primary Rat Neurons[J]. PLOS ONE,2015,10(5).
APA	Lei, Yun.,Yang, Ling.,Ye, Chun Yan.,Qin, Ming Yan.,Yang, Huai Yu.,...&Zhang, Hai Yan.(2015).Involvement of Intracellular and Mitochondrial A beta in the Ameliorative Effects of Huperzine A against Oligomeric A beta(42)-Induced Injury in Primary Rat Neurons.PLOS ONE,10(5).
MLA	Lei, Yun,et al."Involvement of Intracellular and Mitochondrial A beta in the Ameliorative Effects of Huperzine A against Oligomeric A beta(42)-Induced Injury in Primary Rat Neurons".PLOS ONE 10.5(2015).