Invited Symposium: Molecular Mechanisms of Ageing
We compared the mechanisms of apolipoprotein E (apoE)- and antioxidant (AO)-mediated inhibition of beta-amyloid fibril (fA-beta) formation in vitro, based on a nucleation-dependent polymerization model using fluorescence spectroscopy with thioflavin T. We first applied a kinetic plot to transform a sigmoidal time-course curve of fA-beta formation from fresh amyloid beta-peptides (A-beta) into a straight line. Mathematical treatment of this plot demonstrated that the above-described sigmoidal curve is a logistic curve and provided us with a kinetic parameter t1/2, the time when the rate of fA-beta formation is maximum. Although apoE extended t1/2 in a dose dependent manner, AO did not. On the other hand, the final amount of fA-beta formed was decreased by both apoE and AO dose-dependently. We then analyzed the effect of apoE and AO on the extension reaction of fA-beta, based on a first-order kinetic model. Although apoE extended the time to proceed to equilibrium in a dose-dependent manner, AO did not. On the other hand, both apoE and AO dose-dependently decreased the final amount of fA-beta formed. These results indicate that apoE and AO inhibit fA-beta formation in vitro by different mechanisms, and suggest the existence of multiple pharmacological targets for the prevention of fA-beta formation in vivo.
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|Naiki, H; (1998). Different Mechanisms of Apolipoprotein E- and Antioxidant-Mediated Inhibition of Alzheimer's beta-Amyloid Fibril Formation in Vitro. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/higuchi/naiki0305/index.html|
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