Neuroprotective effects of estradiol in mesencephalic dopaminergic neurons

There is a gender difference, or male predominance, in Parkinson's disease and attention deficit hyperactivity disorder (ADHD). Although the reason why it is predominantly the male who suffers from the diseases is still unknown, the female steroid hormone may be involved in the pathogenesis. Estrogen is a female sex hormone with a steroid structure. Like other steroid hormones, it binds to specific receptors in the nuclei and regulates gene transcription (genomic effects). In addition to the genomic effects, it can act as an antioxidant, a process not mediated by the estrogen receptor (nongenomic effects). Further, estrogen can have a novel action through a specific receptor located in the plasma membrane. In the central nervous system, estrogen provides neuroprotection mediated through multiple mechanisms. In this article, we review several possible mechanisms for the neuroprotective effects including antiapoptotic protection by estrogens as transcription factors, protection against oxidative stress by estrogens acting as antioxidants, and neurotrophic cross talk through the signal cascade shared with neurotrophic factors.