Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38 |
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Authors: | Vallés Soraya L Borrás Consuelo Gambini Juan Furriol Jessica Ortega Angel Sastre Juan Pallardó Federico V Viña Jose |
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Affiliation: | Department of Physiology, University of Valencia, School of Medicine, Valencia, Spain; Fundación Hospital Clínico Universitario de Valencia, Valencia, Spain |
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Abstract: | Oestrogenic compounds have been postulated as neuroprotective agents. This prompted us to investigate their mechanism action in neurons in primary culture. Cells were pretreated with physiological concentrations of 17-β estradiol (0.2 n m ) or with nutritionally relevant concentrations of genistein (0.5 µ m ), and 48 h later treated with 5 µ m of amyloid beta (Aβ) for 24 h. We found that Aβ increased oxidative stress, measured as peroxide levels or oxidized glutathione/reduced glutathione ratio, which in turn, caused phosphorylation of p38 MAP kinase. Amyloid beta subsequently induced neuronal death. Inhibiting the MAP kinase pathway prevented cell death, confirming the role of p38 in the toxic effect of Aβ. All these effects were prevented when cells were pretreated for 48 h with oestradiol or genistein. Therefore, oestrogenic compounds rescue neurons from Aβ-induced cell death by preventing oxidative stress, which in turn inhibits the activation of p38, protecting neurons from cell death. Because hormone replacement therapy with oestradiol could cause serious setbacks, the potential therapeutic effect of phyto-oestrogens for the prevention of Aβ-associated neurodegenerative disorders should be more carefully studied in clinical research. |
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Keywords: | Alzheimer's disease amyloid beta toxicity oestrogenic compounds oxidative stress signalling |
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