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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid beta-Peptides / antagonists & inhibitors
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Animals
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Brain / drug effects
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Brain / metabolism
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Cells, Cultured
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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Estradiol / metabolism
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Estradiol / pharmacology
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Estradiol Congeners / pharmacology*
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Estrogen Receptor alpha / agonists
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor beta / agonists
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Estrogen Receptor beta / metabolism
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Estrogens / metabolism*
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Estrogens / pharmacology
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Neurons / drug effects*
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Neurons / physiology
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Neuroprotective Agents / pharmacology*
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Nitriles / pharmacology
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Phenols
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Propionates / pharmacology
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Protein Kinase C / drug effects
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Protein Kinase C / metabolism*
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Pyrazoles / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Estrogen / agonists*
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Receptors, Estrogen / metabolism
Substances
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2,3-bis(4-hydroxyphenyl)-propionitrile
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Amyloid beta-Peptides
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Enzyme Inhibitors
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Estradiol Congeners
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Estrogens
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Neuroprotective Agents
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Nitriles
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Phenols
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Propionates
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Pyrazoles
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Receptors, Estrogen
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4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
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Estradiol
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Protein Kinase C