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http://hdl.handle.net/10261/111881
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dc.contributor.author | Buendía Abaitua, Izaskun | - |
dc.contributor.author | Egea Maiquez, Javier | - |
dc.contributor.author | Parada, Esther | - |
dc.contributor.author | Navarro, Elisa | - |
dc.contributor.author | León, Rafael | - |
dc.contributor.author | Rodríguez-Franco, María Isabel | - |
dc.contributor.author | López, M. G. | - |
dc.date.accessioned | 2015-03-05T11:56:52Z | - |
dc.date.available | 2015-03-05T11:56:52Z | - |
dc.date.issued | 2015 | - |
dc.identifier | doi: 10.1021/cn5002073 | - |
dc.identifier | issn: 1948-7193 | - |
dc.identifier | e-issn: 1948-7193 | - |
dc.identifier.citation | ACS Chemical Neuroscience 6: 288-296 (2015) | - |
dc.identifier.uri | http://hdl.handle.net/10261/111881 | - |
dc.description.abstract | We have investigated the protective effects of ITH91/IQM157, a hybrid of melatonin and N,N-dibenzyl(N-methyl)amine, in an in vitro model of Alzheimer's disease (AD)-like pathology that combines amyloid beta (Aβ) and tau hyperphosphorylation induced by okadaic acid (OA), in the human neuroblastoma cell line SH-SY5Y. Combination of subtoxic concentrations of Aβ and OA caused a significant toxicity of 40% cell death, which mainly was apoptotic; this effect was accompanied by retraction of the cells' prolongations and accumulation of thioflavin-S stained protein aggregates. In this toxicity model, ITH91/IQM157 (1-1000 nM) reduced cell death measured as MTT reduction; at 100 nM, it prevented apoptosis, retraction of prolongations, and Aβ aggregates. The protective actions of ITH91/IQM157 were blocked by mecamylamine, luzindol, chelerythrine, PD98059, LY294002, and SnPP. We show that the combination of melatonin with a fragment endowed with AChE inhibition in a unique chemical structure, ITH91/IQM157, can reduce neuronal cell death induced by Aβ and OA by a signaling pathway that implicates both nicotinic and melatonin receptors, PKC, Akt, ERK1/2, and induction of hemoxygenase-1. | - |
dc.publisher | American Chemical Society | - |
dc.relation | eu-repo/grant/Agreement/EC/FP7/322156 | - |
dc.relation.isversionof | Preprint | - |
dc.rights | openAccess | - |
dc.title | The melatonin- N,N-dibenzyl(N-methyl)amine hybrid ITH91/IQM157 affords neuroprotection in an in vitro Alzheimer's model via hemo-oxygenase-1 induction | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1021/cn5002073 | - |
dc.date.updated | 2015-03-05T11:56:52Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.contributor.funder | European Commission | - |
dc.contributor.funder | Instituto de Salud Carlos III | - |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | - |
dc.contributor.funder | Universidad Autónoma de Madrid | - |
dc.contributor.funder | Instituto Fundación Teófilo Hernando | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004587 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004593 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
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The melatonin-NN-dibenzyl(N-methyl)amine hybrid.pdf | 869,26 kB | Adobe PDF | Visualizar/Abrir |
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