Estrogen has anti-amyloidogenic effects on Alzheimer's beta-amyloid fibrils in vitro.
Inhibition of the assembly of amyloid beta-peptide (Abeta) as well as the destabilization of preformed beta-amyloid fibrils (fAbeta) in the central nervous system could be 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 fAbeta(1-42) and fAbeta(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 fAbetas. 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.
Morinaga
Akiyoshi
A
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Hirohata
Mie
M
Ono
Kenjiro
K
Yamada
Masahito
M
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology*; D008854:Microscopy, Electron; D015394:Molecular Structure; D010446:Peptide Fragments / Q000378:metabolism
D016229:Amyloid beta-Peptides; D004967:Estrogens; D010446:Peptide Fragments