Amyloid β cytotoxicity is enhanced or reduced depending on formation of amyloid β oligomeric forms.

Abstract

We explored the underlying mechanisms that facilitate reducing and enhancing effects of exogenous proteins on cytotoxicity of amyloid β (Aβ), a main pathogen of Alzheimer's disease, by using an Escherichia coli chaperonin DnaK. DnaK was chosen as a tool, because it, easily available and functionally stable, reduced or enhanced Aβ cytotoxicity depending on its concentration. Cytotoxicity was enhanced when the molar ratio of DnaK to Aβ42, at 20μM Aβ42, was 0.01-0.5, while reduced cytotoxicity was observed at higher ratios (> 1) at 1μM Aβ42. Significant amounts of oligomeric Aβ42 species accumulated concomitantly with enhanced cytotoxicity, whereas the oligomers appeared to form complexes with DnaK in conditions of reduced cytotoxicity. The difference in cytotoxicity was due to variations in the toxic oligomeric Aβ species and DnaK is a useful tool for the study of the Aβ ultrastructure formation and toxicity of Aβ peptide.