Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets

	Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets
	Zhao, YM; Dou, J; Luo, JL; Li, WM; Chan, HHN; Cui, W; Zhang, H; Han, RW; Carlier, PR; Zhang, XJ
刊名	BRAIN RESEARCH
	2011
卷号	1421 期号:1 页码:100-109
关键词	Bis(12)-hupyridone NMDA receptor Ischemia Stroke Neuroprotectant
通讯作者	Han, YF (reprint author), Hong Kong Polytech Univ, Inst Modern Med, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China.,bcyfhan@polyu.edu.hk
英文摘要	The activation of N-methyl-D-aspartate (NMDA) receptors by excessive release of glutamate is involved in the pathogenesis of ischemic stroke. Thus the NMDA receptor has become an attractive therapeutic target for the development of neuroprotectants, especially from antagonists with moderate to low affinity. In the current study, NMDA receptor blockage and neuroprotective effects of bis(12)-hupyridone (B12H), a novel dimeric acetylcholinesterase inhibitor derived from a naturally occurring monomeric analog huperzine A, were investigated in vitro and in vivo. In primary rat cerebellar granule neurons, B12H (0.1 nM to 1 mu M) prevented glutamate-induced apoptosis in a concentration- and time-dependent manner. Receptor-ligand binding analysis showed that B12H competed with [(3)H]MK801 with a K(i) value of 7.7 mu M. In the 2-hour middle cerebral artery occlusion rat model, B12H (0.4 and 0.8 mg/kg, 30 min before-ischemia and 15 min post-ischemia, i.p.) significantly attenuated ischemia-induced apoptosis in the penumbra region, improved neurological behavior impairment, and decreased cerebral infarct volume, cerebral edema and neuronal apoptosis in the stroke model. Together, these results showed that B12H moderately blocks NMDA receptors at MK801 site and exerts neuroprotection against excitotoxic and ischemic insults in vitro and in vivo. Combined with our previous publications, we conjecture that B12H might exert neuroprotection via acting on multiple targets. (C) 2011 Elsevier B.V. All rights reserved.
学科主题	Neurosciences & Neurology
类目[WOS]	Neurosciences
关键词[WOS]	NMDA RECEPTOR ANTAGONIST ; FOCAL CEREBRAL-ISCHEMIA ; D-ASPARTATE RECEPTORS ; ALZHEIMERS-DISEASE ; HUPERZINE-A ; PARADIGM SHIFT ; BRAIN-DAMAGE ; MEMANTINE ; BIS(7)-TACRINE ; INHIBITION
收录类别	SCI
语种	英语
WOS记录号	WOS:000297487400011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/909]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhao, YM,Dou, J,Luo, JL,et al. Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets[J]. BRAIN RESEARCH,2011,1421(1):100-109.
APA	Zhao, YM.,Dou, J.,Luo, JL.,Li, WM.,Chan, HHN.,...&Han, YF.(2011).Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets.BRAIN RESEARCH,1421(1),100-109.
MLA	Zhao, YM,et al."Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets".BRAIN RESEARCH 1421.1(2011):100-109.