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Estrogen and Selective Estrogen Receptor Modulators Exert Neuroprotective Effects and Stimulate the Expression of Selective Alzheimer’s Disease Indicator-1 , a Recently Discovered Antiapoptotic Gene, in Human Neuroblast Long-Term Cell Cultures

2005; Oxford University Press; Volume: 90; Issue: 3 Linguagem: Inglês

10.1210/jc.2004-0066

1945-7197

Susanna Benvenuti, Paola Luciani, Gabriella Barbara Vannelli, Stefania Gelmini, Elisa Franceschi, Mario Serio, Alessandro Peri,

Retinoids in leukemia and cellular processes

According to the fact that Alzheimer's disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. Experimental studies, still mostly performed using animal models, demonstrated that estrogen exerts neuroprotective effects. We previously established neuroblast long-term cell cultures from human fetal olfactory epithelium. In the present study, we addressed the role of estrogen in these unique human cells, which express both the estrogen receptor (ER)-α and ERβ. We found that 17β-estradiol (17βE2) and the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen exerted neuroprotective effects, which were independent of cell proliferation, by increasing resistance against β-amyloid-induced toxicity, with the exception of the highest concentrations of raloxifene (10 and 100 nm). In addition, 17βE2 exposure protected from oxidative stress, reduced apoptosis, and increased the expression of the catalytic subunit of telomerase. Furthermore, we evaluated by quantitative real-time RT-PCR whether estrogen/SERMs modulate the expression of the recently discovered seladin-1 (selective AD indicator-1) gene, which exerts neuroprotective effects and is down-regulated in AD-vulnerable brain regions. 17βE2 (100 pm to 100 nm) and SERMs (1 nm) significantly increased the amount of seladin-1 mRNA. Conversely, 10 and 100 nm raloxifene reduced the expression of seladin-1. The effect of estrogen appears mainly mediated by ERα because the selective ERα agonist propylpyrazole-triol determined a much greater increase of seladin-1 expression than the ERβ agonist diarylpropionitrile. Our results add new evidence, using human neuronal cells, for a beneficial effect of estrogen in preventing neurodegenerative diseases and suggest for the first time that seladin-1 may mediate this effect.