The fertile period of women's life compared to menopause is associated with a lower incidence of degenerative inflammatory diseases. In brain, estrogens ameliorate brain performance and have positive effects on selected neural pathologies characterized by a strong inflammatory component. We thus hypothesized that the inflammatory response is a target of estrogen action; several studies including ours provided strong evidence to support this prediction. Microglia, the brain's inflammatory cells, and circulating monocytes express the estrogen receptors ER-alpha and ER-beta and their responsiveness in vivo and in vitro to pro-inflammatory agents, such as lipopolysaccharide (LPS), is controlled by 17beta-estradiol (E(2)). Susceptibility of central nervous system (CNS) macrophage cells to E(2) is also preserved in animal models of neuroinflammatory diseases, in which ER-alpha seems to be specifically involved. At the molecular level, induction of inflammatory gene expression is blocked by E(2). We recently observed that, differently from conventional anti-inflammatory drugs, E(2) stimulates a nongenomic event that interferes with the LPS signal transduction from the plasma membrane to cytoskeleton and intracellular effectors, which results in the inhibition of the nuclear translocation of NF-kappaB, a transcription factor of inflammatory genes. Interference with NF-kappaB intracellular trafficking is selectively mediated by ER-alpha. In summary, evidence from basic research strongly indicates that the use of estrogenic drugs that can mimic the anti-inflammatory activity of E(2) might trigger beneficial effects against neurodegeneration in addition to carrying out their specific therapeutic function

Estrogen action in neuroprotection and brain inflammation / S. Pozzi, V. Benedusi, A. Maggi, E. Vegeto. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - 1089(2006 Nov), pp. 302-323. [10.1196/annals.1386.035]

Estrogen action in neuroprotection and brain inflammation

S. Pozzi
Primo
;
V. Benedusi
Secondo
;
A. Maggi
Penultimo
;
E. Vegeto
Ultimo
2006-11

Abstract

The fertile period of women's life compared to menopause is associated with a lower incidence of degenerative inflammatory diseases. In brain, estrogens ameliorate brain performance and have positive effects on selected neural pathologies characterized by a strong inflammatory component. We thus hypothesized that the inflammatory response is a target of estrogen action; several studies including ours provided strong evidence to support this prediction. Microglia, the brain's inflammatory cells, and circulating monocytes express the estrogen receptors ER-alpha and ER-beta and their responsiveness in vivo and in vitro to pro-inflammatory agents, such as lipopolysaccharide (LPS), is controlled by 17beta-estradiol (E(2)). Susceptibility of central nervous system (CNS) macrophage cells to E(2) is also preserved in animal models of neuroinflammatory diseases, in which ER-alpha seems to be specifically involved. At the molecular level, induction of inflammatory gene expression is blocked by E(2). We recently observed that, differently from conventional anti-inflammatory drugs, E(2) stimulates a nongenomic event that interferes with the LPS signal transduction from the plasma membrane to cytoskeleton and intracellular effectors, which results in the inhibition of the nuclear translocation of NF-kappaB, a transcription factor of inflammatory genes. Interference with NF-kappaB intracellular trafficking is selectively mediated by ER-alpha. In summary, evidence from basic research strongly indicates that the use of estrogenic drugs that can mimic the anti-inflammatory activity of E(2) might trigger beneficial effects against neurodegeneration in addition to carrying out their specific therapeutic function
Estrogen receptors; Inflammation; Neurodegeneration
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/43101
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