title: Estrogen action in neuroprotection and brain inflammation.
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.
authors.affiliation: Center of Excellence on Neurodegenerative Diseases, Department of Pharmacological Sciences, University of Milan, Via Balzaretti, 9, 20133 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pozzi
authors.forename: Valeria
authors.initials: V
authors.lastname: Benedusi
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Vegeto
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000502:physiology; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D004967:Estrogens / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats
chemical_list: D004967:Estrogens; D018696:Neuroprotective Agents