Polycyclic phenols, estrogens and neuroprotection: a proposed mitochondrial mechanism.
Polycyclic phenols, including the estrogens, have been shown to be potent neuroprotectants in a variety of cellular and animal model systems. Although classical estrogen receptor interactions and consequent responses play a role in certain circumstances, the neuroprotective activity of polycyclic phenols that do not interact with estrogen receptors ERalpha or ERbeta is more likely to be through non-genomic mechanism(s). We propose here that such non-feminizing polycyclic phenols exert their protective effects at least in part by stabilizing mitochondria, preventing apoptotic and/or necrotic forms of cell death that are associated with mitochondrial dysfunction. Consistent with this mitochondrial model and the available data, these compounds protect neurons and other cell types from a wide variety of pathologically relevant stressors.
Dykens
J A
JA
MitoKor Inc., 11494 Sorrento Valley Road, San Diego, CA 92121, USA.
Simpkins
J W
JW
Wang
J
J
Gordon
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000927:Anticonvulsants / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds; D010636:Phenols / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D010636:Phenols; D011422:Propionates; D004958:Estradiol; D000255:Adenosine Triphosphate; C015392:3-nitropropionic acid; D002118:Calcium