1. Multiple pathways transmit neuroprotective effects of gonadal steroids.
- Author
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Bryant DN, Sheldahl LC, Marriott LK, Shapiro RA, and Dorsa DM
- Subjects
- Animals, Brain Injuries drug therapy, Brain Injuries metabolism, Estradiol pharmacology, Estrogen Replacement Therapy, Gonadal Steroid Hormones pharmacology, Membrane Proteins metabolism, Models, Biological, Nervous System Diseases prevention & control, Neuroprotective Agents pharmacology, Protein Processing, Post-Translational drug effects, Receptors, Estrogen metabolism, Regulatory Elements, Transcriptional, Sex Characteristics, Estradiol physiology, Gene Expression Regulation drug effects, Gonadal Steroid Hormones physiology, Signal Transduction drug effects
- Abstract
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.
- Published
- 2006
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