title: Effects of sex hormones on Alzheimer's disease-associated β-amyloid oligomer formation in vitro.
abstract: The folding of amyloid β-protein (Aβ) into oligomeric, protofibrillar, and fibrillar assemblies is hypothesized to be the key pathogenic event in Alzheimer's disease (AD), with oligomeric assemblies thought to be the most neurotoxic. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for patients with AD. Epidemiological studies have indicated that estrogen therapy reduces 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 in vitro oligomer formation of Aβ(1-40) and Aβ(1-42) using a method of photo-induced cross-linking of unmodified proteins (PICUP) and electron microscopic studies. Estrogens (E1, E2, and E3) inhibited low-order Aβ oligomer formation, and among them, E3 had the strongest in vitro activity. Estrogen could be a potential therapeutic agent to prevent or delay AD progression, and further understanding of the fact that these very similar molecules have different anti-oligomeric effects would contribute to the development of new agents.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Morinaga
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Junichi
authors.initials: J
authors.lastname: Takasaki
authors.forename: Tokuhei
authors.initials: T
authors.lastname: Ikeda
authors.forename: Mie
authors.initials: M
authors.lastname: Hirohata
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000172:deficiency / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000378:metabolism*; D017698:Postmenopause / Q000187:drug effects / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D012739:Gonadal Steroid Hormones