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Estrogen receptor-mediated neuroprotection: The role of the Alzheimer's disease-related gene seladin-1.

Peri A, Serio M - Neuropsychiatr Dis Treat (2008)

Bottom Line: Seladin-1 has been found to be identical to the gene encoding the enzyme 3-beta-hydroxysterol delta-24-reductase, involved in the cholesterol biosynthetic pathway, which confers protection against beta-amyloid-mediated toxicity and from oxidative stress, and is an effective inhibitor of caspase-3 activity, a key mediator of apoptosis.Interestingly, we found earlier that the expression of this gene is up-regulated by estrogen.This review will summarize the current knowledge regarding the neuroprotective effects of seladin-1 and the relationship between this protein and estrogen.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Physiopathology, Endocrine Unit, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOThe), University of Florence Florence, Italy.

ABSTRACT
Experimental evidence supports a protective role of estrogen in the brain. According to the fact that Alzheimer's disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. However, there is no general consensus on the beneficial effect of estrogen or selective estrogen receptor modulators in preventing or treating AD. It has to be said that several factors may markedly affect the efficacy of the treatment. A few years ago, the seladin-1 gene (for selective Alzheimer's disease indicator-1) has been isolated and found to be down-regulated in brain regions affected by AD. Seladin-1 has been found to be identical to the gene encoding the enzyme 3-beta-hydroxysterol delta-24-reductase, involved in the cholesterol biosynthetic pathway, which confers protection against beta-amyloid-mediated toxicity and from oxidative stress, and is an effective inhibitor of caspase-3 activity, a key mediator of apoptosis. Interestingly, we found earlier that the expression of this gene is up-regulated by estrogen. Furthermore, our very recent data support the hypothesis that seladin-1 is a mediator of the neuroprotective effects of estrogen. This review will summarize the current knowledge regarding the neuroprotective effects of seladin-1 and the relationship between this protein and estrogen.

No MeSH data available.


Related in: MedlinePlus

Effect of different concentrations of raloxifene on β-amyloid (βA) (10 and 100 nM) toxicity, as assessed by MTS assay (Promega Corp., Madison, WI).Notes: *p < 0.05 versus control cells not exposed to β-amyloid (black bars). Modified with permission from Benvenuti S, Luciani P, Vannelli GB, et al 2005. Estrogen and SERMs exert neuroprotective effects and stimulate the expression of seladin-1, a recently discovered anti-apoptotic gene, in human neuroblast long-term cell cultures. J Clin Endocrinol Metab, 90:1775–82.
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fig2: Effect of different concentrations of raloxifene on β-amyloid (βA) (10 and 100 nM) toxicity, as assessed by MTS assay (Promega Corp., Madison, WI).Notes: *p < 0.05 versus control cells not exposed to β-amyloid (black bars). Modified with permission from Benvenuti S, Luciani P, Vannelli GB, et al 2005. Estrogen and SERMs exert neuroprotective effects and stimulate the expression of seladin-1, a recently discovered anti-apoptotic gene, in human neuroblast long-term cell cultures. J Clin Endocrinol Metab, 90:1775–82.

Mentions: Our findings confirmed the protective role of estrogen/SERMs in the brain. In fact, we observed that, whereas in the absence of estrogen pre-incubation β-amyloid (10 and 100 nM) and H2O2 (200 μM) significantly reduced cell viability, the pre-treatment with 17β-estradiol (100 pM–100 nM) effectively counteracted β-amyloid- or oxidative stress-induced toxicity (Benvenuti et al 2005). In agreement with estrogen, also the SERM tamoxifen (100 pM–100 nM) effectively protected FNC cells from the toxic effects of β-amyloid, whereas partially different results were observed using raloxifene. In fact, cell viability after exposure to β-amyloid was preserved at low concentrations of raloxifene (100 pM and 1 nM). Conversely, 10 and 100 nM did not exert protective effects (Figure 2). In addition, we demonstrated that the protective action of estrogen in FNC cells was associated to a counteracting effect against β-amyloid-induced apoptosis, as demonstrated by the strong inhibition of the activation of caspase-3.


Estrogen receptor-mediated neuroprotection: The role of the Alzheimer's disease-related gene seladin-1.

Peri A, Serio M - Neuropsychiatr Dis Treat (2008)

Effect of different concentrations of raloxifene on β-amyloid (βA) (10 and 100 nM) toxicity, as assessed by MTS assay (Promega Corp., Madison, WI).Notes: *p < 0.05 versus control cells not exposed to β-amyloid (black bars). Modified with permission from Benvenuti S, Luciani P, Vannelli GB, et al 2005. Estrogen and SERMs exert neuroprotective effects and stimulate the expression of seladin-1, a recently discovered anti-apoptotic gene, in human neuroblast long-term cell cultures. J Clin Endocrinol Metab, 90:1775–82.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2536547&req=5

fig2: Effect of different concentrations of raloxifene on β-amyloid (βA) (10 and 100 nM) toxicity, as assessed by MTS assay (Promega Corp., Madison, WI).Notes: *p < 0.05 versus control cells not exposed to β-amyloid (black bars). Modified with permission from Benvenuti S, Luciani P, Vannelli GB, et al 2005. Estrogen and SERMs exert neuroprotective effects and stimulate the expression of seladin-1, a recently discovered anti-apoptotic gene, in human neuroblast long-term cell cultures. J Clin Endocrinol Metab, 90:1775–82.
Mentions: Our findings confirmed the protective role of estrogen/SERMs in the brain. In fact, we observed that, whereas in the absence of estrogen pre-incubation β-amyloid (10 and 100 nM) and H2O2 (200 μM) significantly reduced cell viability, the pre-treatment with 17β-estradiol (100 pM–100 nM) effectively counteracted β-amyloid- or oxidative stress-induced toxicity (Benvenuti et al 2005). In agreement with estrogen, also the SERM tamoxifen (100 pM–100 nM) effectively protected FNC cells from the toxic effects of β-amyloid, whereas partially different results were observed using raloxifene. In fact, cell viability after exposure to β-amyloid was preserved at low concentrations of raloxifene (100 pM and 1 nM). Conversely, 10 and 100 nM did not exert protective effects (Figure 2). In addition, we demonstrated that the protective action of estrogen in FNC cells was associated to a counteracting effect against β-amyloid-induced apoptosis, as demonstrated by the strong inhibition of the activation of caspase-3.

Bottom Line: Seladin-1 has been found to be identical to the gene encoding the enzyme 3-beta-hydroxysterol delta-24-reductase, involved in the cholesterol biosynthetic pathway, which confers protection against beta-amyloid-mediated toxicity and from oxidative stress, and is an effective inhibitor of caspase-3 activity, a key mediator of apoptosis.Interestingly, we found earlier that the expression of this gene is up-regulated by estrogen.This review will summarize the current knowledge regarding the neuroprotective effects of seladin-1 and the relationship between this protein and estrogen.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Physiopathology, Endocrine Unit, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOThe), University of Florence Florence, Italy.

ABSTRACT
Experimental evidence supports a protective role of estrogen in the brain. According to the fact that Alzheimer's disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. However, there is no general consensus on the beneficial effect of estrogen or selective estrogen receptor modulators in preventing or treating AD. It has to be said that several factors may markedly affect the efficacy of the treatment. A few years ago, the seladin-1 gene (for selective Alzheimer's disease indicator-1) has been isolated and found to be down-regulated in brain regions affected by AD. Seladin-1 has been found to be identical to the gene encoding the enzyme 3-beta-hydroxysterol delta-24-reductase, involved in the cholesterol biosynthetic pathway, which confers protection against beta-amyloid-mediated toxicity and from oxidative stress, and is an effective inhibitor of caspase-3 activity, a key mediator of apoptosis. Interestingly, we found earlier that the expression of this gene is up-regulated by estrogen. Furthermore, our very recent data support the hypothesis that seladin-1 is a mediator of the neuroprotective effects of estrogen. This review will summarize the current knowledge regarding the neuroprotective effects of seladin-1 and the relationship between this protein and estrogen.

No MeSH data available.


Related in: MedlinePlus