An autocatalytic reaction as a model for the kinetics of the aggregation of beta-amyloid.
Alzheimer's disease is the commonest form of senile dementia, affecting almost 20 million people worldwide. This neurodegenerative disorder is characterized by amyloid deposition in senile plaques, composed primarily of fibrils of an aggregated peptide, beta-amyloid. Fibrillation of beta-amyloid is a nucleation-dependent polymerization process, which is controlled by two kinetics parameters: the nucleation rate and the elongation or growth rate. As the kinetics of fibrillation is strongly dependent on the presence of trace amounts of fibrils, we suggest that the aggregation of beta-amyloid is a model of autocatalytic reaction. A mathematical analysis, permitting quantitative monitoring of the kinetics of fibrillogenesis of beta-amyloid, nucleation, and elongation constants, is presented. The model was checked by applying it to the aggregation of the fragment 1-40 of the beta-amyloid. Understanding of these rate constants may facilitate the study of the effect of substances used for controlling fibril creation and growth. The disaggregating effect of dodecyl trimethylammonium bromide, a cationic surfactant, was easily quantified by means of the model.
Sabaté
Raimon
R
Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Gallardo
Montserrat
M
Estelrich
Joan
J
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D013501:Surface-Active Agents / Q000494:pharmacology; D013997:Time Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013501:Surface-Active Agents; C078592:amyloid beta-protein (1-40)