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• W1535209063 startingPage "1264" @default.
• W1535209063 abstract "Background and purpose: Nebivolol, a selective β 1 ‐adrenoceptor antagonist mediating rapid vasodilating effects, is used clinically to treat hypertension. Recently, it was reported that nebivolol also acts as an oestrogen receptor (ER) agonist. To investigate the neuroprotective potential of oestrogens, we assessed the oestrogenic effects of nebivolol in several in vitro neuronal models. Experimental approach: Human neuroepithelioma SK‐N‐MC cells stably transfected with human ER α and β, and mouse N2A neuroblastoma cells expressing human APP695 SWE [N2Aswe, stably transfected with the Swedish mutation form of the Alzheimer‐associated amyloid precursor protein (APPswe, K670M/N671L)] were incubated with different concentrations of nebivolol and 17β‐oestradiol (E2) for 24–48 h. ER activation was detected in a specific reporter assay, and ER‐dependent gene expression was measured by quantitative real‐time PCR (qRT PCR). Furthermore, cell survival rates were determined, and oxidative stress was induced by hydrogen peroxide and paraquat. Amyloid β protein precursor (APP) processing was investigated, and the cleavage fragments sAPPα and Aβ were quantified via α‐, β‐ and γ‐secretase activity assays. Alterations of secretase expression levels were determined by qRT PCR. Key results: Nebivolol induces oestrogen‐dependent gene transcription, and protects neuronal cells against oxidative stress even at low and physiological concentrations (10 −8 M). Moreover, nebivolol modulates processing of APP in mouse neuronal N2Aswe cells by increasing α‐secretase activity, ultimately leading to enhanced release of soluble non‐amyloidogenic sAPPα. Conclusions and implications: We showed that nebivolol acts as ER agonist in neuronal cell lines, and suggest oestrogen‐like neuroprotective effects mediated by nebivolol." @default.
• W1535209063 created "2016-06-24" @default.
• W1535209063 creator A5019893954 @default.
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• W1535209063 date "2010-03-01" @default.
• W1535209063 modified "2023-10-18" @default.
• W1535209063 title "The selective β1-adrenoceptor antagonist nebivolol is a potential oestrogen receptor agonist with neuroprotective abilities" @default.
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• W1535209063 doi "https://doi.org/10.1111/j.1476-5381.2009.00610.x" @default.
• W1535209063 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2848930" @default.
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