Estrogen has anti-amyloidogenic effects on Alzheimer's beta-amyloid fibrils in vitro

摘要

Inhibition of the assembly of amyloid beta-peptide (A beta) as well as the destabilization of preformed beta-amyloid fibrils (fA beta) in the central nervous system could e valuable therapeutics of patients with Alzheimer's disease (AD). Epidemiological studies have indicated that estrogen therapy reduced the risk of developing AD in women. Here, we examined the effects of estrogen (estrone (E1), estradiol (E2), and estriol (E3)) and related sexual steroids (androstenedione (AND) and testosterone (TES)) on the polymerization, extension and destabilization of fA beta(1-42) and fA beta(1-40) at pH 7.5 at 37 degrees C in vitro, using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies. E1, E2, and E3 dose-dependently inhibited the formation, as well as destabilization of fA beta s. The overall anti-amyloidogenic activity of these molecules was in the order of: E3 > E2 = E1 AND = TES. Estrogen could be a potential therapeutic agent to prevent or delay AD progression. (c) 2007 Elsevier Inc. All rights reserved.