Neuroprotective effects of estrogens: potential mechanisms of action

Epidemiological studies associate post-menopausal estrogen use with a reduc tion in risk of Alzheimer's disease, a reduction in risk of Parkinson's dis ease, 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 mo del systems with toxicities including serum-deprivation, P-amyloid-induced toxicity, excitotoxicity, and oxidative stress. In animal models, estrogens have been shown to attenuate neuronal death in rodent models of cerebral i schemia, traumatic injury, and Parkinson's disease. Although estrogens are known to exert several direct effects on neurons, the cellular mechanisms b ehind the neuroprotective efficacy of the steroid are only beginning to be elucidated. In this review, we summarize the data supporting a neuroprotect ive role for estrogens in both culture and animal models and discuss neuron al 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 activa ted kinase pathway, activation of cAMP signal transduction pathways, modula tion of intracellular calcium homeostasis, and direct antioxidant activity. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved.