Neuroprotective effects of estrogens: potential mechanisms of action
Abstract
Epidemiological studies associate post-menopausal estrogen use with a reduction in risk of Alzheimer's disease, a reduction in risk of Parkinson's disease, and death from stroke. The neuroprotective efficacy of estrogens have been well described and may contribute to these clinical effects. Estrogen-mediated neuroprotection has been described in several neuronal culture model systems with toxicities including serum-deprivation, beta-amyloid-induced toxicity, excitotoxicity, and oxidative stress. In animal models, estrogens have been shown to attenuate neuronal death in rodent models of cerebral ischemia, traumatic injury, and Parkinson's disease. Although estrogens are known to exert several direct effects on neurons, the cellular mechanisms behind the neuroprotective efficacy of the steroid are only beginning to be elucidated. In this review, we summarize the data supporting a neuroprotective role for estrogens in both culture and animal models and discuss neuronal effects of estrogens that may contribute to the neuroprotective effects. These effects include activation of the nuclear estrogen receptor, altered expression of bcl-2 and related proteins, activation of the mitogen activated kinase pathway, activation of cAMP signal transduction pathways, modulation of intracellular calcium homeostasis, and direct antioxidant activity.
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Self-citation
- Authors
- Green, P. S., & Simpkins, J. W.
- Affiliations
- University of Florida (US)
- Corresponding author
- Simpkins, James W.
- Venue
- International Journal of Developmental Neuroscience
- Publisher
- Wiley
- Published
- 2000-05-15
- Volume
- 18
- Issue
- 4-5
- Pages
- 347-358
- ISSN
- 0736-5748 (ISSN-L)
- 1873-474X
- OpenAlex
- W2043348076
- Cited by
- 523
- References
- 150
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 10 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 10 · 2018: 15 · 2017: 10 · 2016: 13 · 2015: 12 · 2014: 24 · 2013: 13 · 2012: 18
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- estrogen neuroprotection, Alzheimer's disease, Parkinson's disease, stroke, estrogen receptor, amyloid-beta toxicity, excitotoxicity, oxidative stress, cerebral ischemia, traumatic brain injury, Bcl-2, mitogen-activated protein kinase, cAMP signaling, intracellular calcium homeostasis, antioxidant activity, hormone replacement therapy
- MeSH terms
- Animals, Brain Chemistry, Estrogens, Female, Humans, Neuroprotective Agents, Neurodegenerative Diseases, Hormone Replacement Therapy
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