Seladin-1 as a target of estrogen receptor activation in the brain: a new gene for a rather old story?
Experimental evidence indicates that estrogen exerts neuroprotective effects. According to the fact that Alzheimer's disease (AD) is more common in post-menopausal women, estrogen treatment has been proposed. However, the beneficial effect of estrogen or selective estrogen receptor modulators (SERMs) in preventing or treating AD is a controversial issue, which will be summarized in this review. Recently, a novel gene, named selective AD indicator-1 (seladin-1), has been isolated and found to be down-regulated in brain regions affected by AD. Seladin-1, which is considered the human homolog of the plant protein DIMINUTO/DWARF1, 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. This review will present the up-to-date findings regarding seladin-1 and DIMINUTO/DWARF1. In addition, the possibility that seladin-1 may be a downstream effector of estrogen receptor activation in the brain, based on our recent experimental findings using a human fetal neuronal model, will be addressed.
Peri
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A
Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies, University of Florence, Italy. a.peri@dfc.unifi.it
Danza
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G
Serio
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M
D000544:Alzheimer Disease / Q000517:prevention & control; D029681:Arabidopsis Proteins / Q000235:genetics; D001921:Brain / Q000502:physiology*; D005260:Female; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018696:Neuroprotective Agents / Q000494:pharmacology; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
D029681:Arabidopsis Proteins; C091574:DIM1 protein, Arabidopsis; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D044925:Oxidoreductases Acting on CH-CH Group Donors; C437069:3beta-hydroxysterol delta24-reductase; C499055:DHCR24 protein, human