Multiple pathways transmit neuroprotective effects of gonadal steroids.
Numerous preclinical studies suggest that gonadal steroids, particularly estrogen, may be neuroprotective against insult or disease progression. This paper reviews the mechanisms contributing to estrogen-mediated neuroprotection. Rapid signaling pathways, such as MAPK, PI3K, Akt, and PKC, are required for estrogen's ability to provide neuroprotection. These rapid signaling pathways converge on genomic pathways to modulate transcription of E2-responsive genes via ERE-dependent and ERE-independent mechanisms. It is clear that both rapid signaling and transcription are important for estrogen's neuroprotective effects. A mechanistic understanding of estrogen-mediated neuroprotection is crucial for the development of therapeutic interventions that enhance quality of life without deleterious side effects.
Bryant
Damani N
DN
Department of Physiology and Pharmacology (L334), Oregon Health & Science University, Portland, OR 97239, USA.
Sheldahl
Laird C
LC
Marriott
Lisa K
LK
Shapiro
Robert A
RA
Dorsa
Daniel M
DM
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D015914:Estrogen Replacement Therapy; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009422:Nervous System Diseases / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects
D012739:Gonadal Steroid Hormones; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D004958:Estradiol