earticle

영어

Amyloid-β peptide (Aβ), implicated in Alzheimer's disease, associates into the fibrils that deposit in senile plaque. The 39~43 amino acid long peptide assemble into various species which could be regulated by chaperone molecules. Despite extensive progress, the results are conflicting; for example, both reduction and enhancement of Aβ cytotoxicity by chaperone have been reported. And the relationship of Aβ structural species with chaperone, and further its implication in cytotoxicity remain to be elucidated. To address this question and to understand the underlying mechanism(s), in this study, the effect of a chaperone molecule, DnaK, on Aβ structure and its effect on cytotoxicity were investigated under several different conditions. A significant amount of oligomeric species of Aβ that is believed to be more toxic among Aβ structures was accumulated at 0.01~0.1 ratio of DnaK/abeta42, while such accumulation was not observed with higher ratio, where the oligomers appeared in the form of complexes with the chaperone molecules. Importantly, accumulation of these Aβ oligomers exerted enhanced toxicity concomitantly and, in contrast, cytoprotection was observed at excess molar of DnaK. In all conditions, fibrillar forms were markedly inhibited. Further, fibrillization kinetics indicated that DnaK might affect on nucleation step, while circular dichroism spectroscopy demonstrated that DnaK delayed overall β- sheet formation. Taken together, results indicate that the chaperone influences Aβ structural transition from oligomer to fibrillar structures as well as from monomer to oligomer with variable rates, and as results, it decreased or increased the amount of Aβ oligomer as well as the cytotoxicity.