Neuroprotective effects of estrogen and selective estrogen receptor modulators begin at the plasma membrane.
Estrogen is neuroprotective in a large number of models in vivo and in vitro. Its application in hormone replacement therapy has proven to be more complicated, necessitating better understanding of how estrogen signals in the brain. Estrogen binds to estrogen receptors to regulate gene transcription, and activates a number of rapid signaling cascades from the plasma membrane. These rapid signaling cascades have been shown to play important roles in mediating the neuroprotective effects of estrogen. This review covers evidence that understanding and targeting the membrane effects of estrogen has emerged as an important area in the design of novel neuroprotective drugs.
Sheldahl
L C
LC
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97236, USA.
Marriott
L K
LK
Bryant
D M
DM
Shapiro
R A
RA
Dorsa
D M
DM
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020521:Stroke / Q000188:drug therapy; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D004967:Estrogens; D018696:Neuroprotective Agents; D020845:Selective Estrogen Receptor Modulators