The Potential for Estrogens in Preventing Alzheimer's Disease and Vascular Dementia

Estrogens are the best-studied class of drugs for potential use in the prevention of Alzheimer's disease (AD). These steroids have been shown to be potent neuroprotectants both in vitro and in vivo, and to exert effects that are consistent with their potential use in prevention of AD. These include the prevention of the processing of amyloid precursor protein (APP) into beta-amyloid (Aß), the reduction in tau hyperphosphorylation, and the elimination of catastrophic attempts at neuronal mitosis. Further, epidemiological data support the efficacy of early postmenopausal use of estrogens for the delay or prevention of AD. Collectively, this evidence supports the further development of estrogen-like compounds for prevention of AD. Several approaches to enhance brain specificity of estrogen action are now underway in an attempt to reduce the side effects of chronic estrogen therapy in AD

Implications for Estrogens in Parkinson’s Disease

Evidence from experimental and epidemiological studies suggests a role of sex hormones in the pathogenic process leading to neurodegenerative diseases, (i.e., Alzheimer's and Parkinson's disease). The effects of sexual steroid hormones are complex and vary with the events of women's fertile life. Estrogens are supposed to influence dopamine synthesis, metabolism, and transport; however, there is no consensus regarding the direction, locus, and mechanism of the effect of estrogens on the dopaminergic system. A neuroprotective effect of estrogens has been demonstrated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-animal models of Parkinson's disease (PD). Epidemiological studies indicate gender differences regarding the onset and the prognosis of PD. Most of the analytical studies explored the relationship between PD and exogenous estrogens. Only three studies investigated the role of endogenous estrogens in the risk of developing PD. These studies reported an increased risk of PD in conditions causing an early reduction in endogenous estrogens (early menopause, reduced fertile life length). Longer cumulative length of pregnancies has also been associated with an increased PD risk. A lack of consensus still exists on the effect of the type of menopause (surgical vs. natural) on PD risk. Finally, the effect of postmenopausal estrogen replacement therapy is still debated. Inconsistencies across studies are in part explained by the complexity of the mechanisms of action of sexual hormones and by the paucity of analytical studies

Studies of plasma performance and transport in the advanced toroidal facility (ATF)

An overview of recent ATF experimental results and program plans is presented, with emphasis on the role of magnetic configuration controls in transport studies. The ATF operating space is bounded by a density limit that effectively sets a limit on the energy confinement time {tau}{sub E}. Although this limit is not solely due to impurities, it has recently been raised by improved cleanliness following titanium gettering. This has led to collapse-free neutral beam injection (NBI) discharges with global {tau}{sub E} {approx} 16 ms. Preliminary experiments show that stored energy and bootstrap current are sensitive to details of the magnetic configuration. 13 refs., 8 figs