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Neuroprotective effects of estrogens: potential mechanisms of action
Author(s) -
Green Pattie S.,
Simpkins James W.
Publication year - 2000
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(00)00017-4
Subject(s) - neuroprotection , estrogen , excitotoxicity , oxidative stress , estrogen receptor , pharmacology , neuroscience , neurodegeneration , medicine , biology , disease , receptor , glutamate receptor , cancer , breast cancer
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, β‐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.