Gonadal steroids are known to be of prime importance in the normal maintenance of brain function. Data from epidemiological studies suggest that the decline in estrogen following menopause may increase the risk of neurodegenerative diseases. There is accumulating epidemiological evidence for neuroprotection by estrogens against neurodegenerative diseases, such as Alzheimer’s disease. Although it is unclear whether estrogen may be effective in preventing further cognitive decline in women who already have Alzheimer’s disease, several studies indicate that estrogen replacement improves the cognitive performance of postmenopausal women. Despite the somewhat controversial data from human studies, experimental investigations in different animals have shown that estrogen is neuroprotective. Although estrogens are known to exert several direct effects on neurons, the cellular mechanisms involved in the neuroprotective effects of estrogen are still unclear. Estrogen causes most of its neuroprotective effects by means of direct binding to specific nuclear receptors. The anti-oxidant effects of estrogens and activation of different membrane-associated intracellular signaling pathways or neurotrophic cross talk through the signal cascade shared with neurotrophic factors could also contribute to neuroprotection. In this article, we outline the evidence supporting a direct role of estrogen in neuronal survival, and explore possible cellular mechanisms for this.

Keywords: Antioxidants - metabolism, Antioxidants - pharmacology, Apolipoproteins E - metabolism, Brain - metabolism, Cell Membrane - metabolism, Estrogens - physiology, Neurodegenerative Diseases - metabolism, Neurons - pathology, Receptors, Estrogen - metabolism