期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：21
页码：12277-12282
DOI：10.1073/pnas.95.21.12277
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Fibrillogenesis of the amyloid {beta}-protein (A{beta}) is believed to play a central role in the pathogenesis of Alzheimer's disease. Previous studies of the kinetics of A{beta} fibrillogenesis showed that the rate of fibril elongation is proportional to the concentration of monomers. We report here the study of the temperature dependence of the A{beta} fibril elongation rate constant, ke, in 0.1 M HCl. The rate of fibril elongation was measured at A{beta} monomer concentrations ranging from 50 to 400 {micro}M and at temperatures from 4{degrees}C to 40{degrees}C. Over this temperature range, ke increases by two orders of magnitude. The temperature dependence of ke follows the Arrhenius law, ke = A exp (-EA/kT). The preexponential factor A and the activation energy EA are {approx}6 x 1018 liter/(mol{middle dot}sec) and 23 kcal/mol, respectively. Such a high value of EA suggests that significant conformational changes are associated with the binding of A{beta} monomers to fibril ends.
