Neuroprotective activities of estrogen: an update

For many molecules, which have been found first in a certain tissue and with a certain activity in the body, multiple activities have been discovered decades later. The steroidal compound estrogen (estradiol) is certainly such a molecule. What was first described as the female sex hormone is now well acknowledged as a central neuroactive and neuromodulatory molecule. One important aspect of estrogen's effects on neurons is its neuroprotective activity. Cellular and molecular studies underline powerful neuroprotective functions of estrogen which are characterized by long-term "classical" genomic effects as well as by rapid activities depending on estrogens interaction with neuronal membranes and intracellular signal transduction pathways. In addition, estrogen has been shown to bear an intrinsic antioxidant structure that lies in the phenolic moiety of the steroidal compound. This antioxidant activity of estrogen and estrogen-derivatives may provide an antioxidant "chemical shield" for neurons and may complement other neuroprotective activities of estrogen and therefore also mediate some of the beneficial effects of estrogen replacement with respect to Alzheimer's Disease. Although, investigated for decades estrogen and its receptors may still hold many surprises that remain to be identified. With the advent of novel genomic techniques, the neuronal target genes of estrogen will be identified in the future.