title: Neuroprotective properties of selective estrogen receptor agonists in cultured neurons.
abstract: To investigate the role of the estrogen receptor (ER) in mediating neuroprotection, the neuroprotective profiles of selective ER agonists for ERalpha and ERbeta, propylpyrazole triol (PPT) and 2,3-bis(4-hydroxyphenyl) proprionitrile (DPN), respectively, were compared to that of 17beta-estradiol and 17alpha-estradiol in primary neuron cultures challenged by beta-amyloid toxicity. All compounds were found to be neuroprotective in an ER-dependent manner. However, protein kinase C (PKC) inhibition completely blocked the protective effects of 17beta-estradiol and 17alpha-estradiol and significantly attenuated PPT but not DPN neuroprotection. These data indicate that estrogen-mediated neuroprotection likely involves a variety of mechanisms and that protection due to PKC activation is more likely due to ERalpha compared to ERbeta.
authors.affiliation: Neuroscience Graduate Program and Andrus Gerontology Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Cordey
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Pike
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D045166:Estradiol Congeners / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000819:agonists* / Q000378:metabolism
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D045166:Estradiol Congeners; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D018696:Neuroprotective Agents; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D011960:Receptors, Estrogen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol; D011493:Protein Kinase C