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Bis(12)-hupyridone, a novel multifunctional dimer, promotes neuronal differentiation more potently than its monomeric natural analog huperzine A possibly through alpha7 nAChR
Cui, Wei2; Cui, Guo-Zhen1; Li, Wenming2; Zhang, Zaijun1; Hu, Shengquan2; Mak, Shinghung2; Zhang, Huan2; Carlier, Paul R.3; Choi, Chung-lit2; Wong, Yi-Tao1; Lee, Simon Ming-Yuen1; Han, Yifan2
2011
Source PublicationBRAIN RESEARCH
ISSN0006-8993
Volume1401Issue:15Pages:10-17
Abstract

The cause of many neurodegenerative disorders can be ascribed to the loss of functional neurons, and thus agents capable of promoting neuronaldifferentiation may have therapeutic benefits to patients of these disorders. In this study, the effects and underlying mechanisms of bis(12)-hupyridone(B12H), a novel dimeric acetylcholinesterase inhibitor modified from huperzine A (HA), on neuronal differentiation were investigated using both the rat PC12 pheochromocytoma cell line and adult rat hippocampus neural stem cells. B12H (3-30 mu M), characterized by morphological changes and expression of GAP-43, induced neurite outgrowth in a concentration- and time-dependent manner, with almost 3-fold higher efficacy than that of HA in PC12 cells. Furthermore, B12H (2.5-10 mu M), but not HA, promoted neuronal differentiation as shown by the percentage increase of beta III-tubulin positive neurons in neural stem cells. The activities of extracellular signal-regulated kinase (ERK), as well as its downstream transcription factors Elk-1 and cAMP response element-binding protein (CREB) were elevated in the B12H-treated PC12 cells. Mitogen-activated protein kinase kinase inhibitors and alpha7-nicotinic acetylcholine receptor (alpha 7nAChR) antagonist blocked the neurite outgrowth and the activation of ERK induced by B12H. All these findings suggest that B12H potently induces pro-neuronal cells into differentiated neurons by activating the ERK pathway possibly via regulating alpha 7nAChR These findings support the recent proposition that alpha 7nAChR is required for the neuronal dendritic arborization and differentiation in the adult mice hippocampus, and provide insights into the possible therapeutic potential of B12H in treating neurodegenerative disorders. (C) 2011 Elsevier B.V. All rights reserved.

KeywordBis(12)-hupyridone Huperzine a Neural Stem Cell Neurodegenerative Disorder Differentiation Alpha 7nachr
DOI10.1016/j.brainres.2011.05.042
URLView the original
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000292941400002
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Cited Times [WOS]:19   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Peoples R China
2.Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Inst Modern Med, Hong Kong, Hong Kong, Peoples R China
3.Virginia Tech, Dept Chem, Blacksburg, VA USA
Recommended Citation
GB/T 7714
Cui, Wei,Cui, Guo-Zhen,Li, Wenming,et al. Bis(12)-hupyridone, a novel multifunctional dimer, promotes neuronal differentiation more potently than its monomeric natural analog huperzine A possibly through alpha7 nAChR[J]. BRAIN RESEARCH,2011,1401(15):10-17.
APA Cui, Wei.,Cui, Guo-Zhen.,Li, Wenming.,Zhang, Zaijun.,Hu, Shengquan.,...&Han, Yifan.(2011).Bis(12)-hupyridone, a novel multifunctional dimer, promotes neuronal differentiation more potently than its monomeric natural analog huperzine A possibly through alpha7 nAChR.BRAIN RESEARCH,1401(15),10-17.
MLA Cui, Wei,et al."Bis(12)-hupyridone, a novel multifunctional dimer, promotes neuronal differentiation more potently than its monomeric natural analog huperzine A possibly through alpha7 nAChR".BRAIN RESEARCH 1401.15(2011):10-17.
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