© 2 0 0 5 , E d i t r i c e K u r t i s 285 J. Endocrinol. Invest. 28: 285-293, 2005 ABSTRACT. 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 β-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.
INTRODUCTIONEpidemiological data, together with experimental and clinical evidence, appear to support a neuroprotective role of estrogen and hormonal therapy in Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in the elderly, has been suggested. However, there is no general consensus on this point, which will be briefly summarized in this review. As a matter of fact, this story is far from being concluded. A debated question concerns the factors which act as downstream mediators of estrogen receptor activation in the brain. The recent identification of the selective AD indicator-1 (seladin-1) gene and the finding that it protects the brain from toxic insults led us to hypothesize that this gene might represent the link between estrogen and neuroprotection. Seladin-1 shares a high degree of sequence homology and some biological functions with a previously identified plant enzyme, named DIMINUTO/DWARF1, which is involved in the biosynthesis of brassinosteroids (BRs), an important class of plant hormones. This review will present the current knowledge on seladin-1 and on its plant homolog DIMINUTO/DWARF1. Furthermore, the possible role of seladin-1 as a target of estrogen receptor activation in the brain, based on our recent experimental findings, will be addressed.
ESTROGEN/SERMS AND NEUROPROTECTION: EX-PERIMENTAL AND CLINICAL EVIDENCEThis topic has been extensively reviewed by many authors and the current experimental and clinical knowledge will be briefly reported in this review. It is well known, based on in vitro evidence, that estrogen exerts neurotrophic and neuroprotective effects by stimulating the expression of neurotrophins and cell-survival factors, enhancing synaptic plasticity and acting as an antioxidant factor (1-3). Besides the hypothalamus, which is the traditional site of estrogen action in the...